Plants: The Potential for Extracting

Protein, Medicines, and Other Useful

Chemicals

September 1983

NTIS order #PB84-114743
Recommended Citation:

Plants: The Potentials for Extracting Protein, Medicines, and Other Useful

Chemicals–Workshop Proceedings (Washington, D. C.: U.S. Congress, Office of Technology Assessment, OTA-BP-F-23, September 1983).

Library of Congress Catalog Card Number 83-600588

For sale by the Superintendent of Documents,

U.S. Government Printing Office, Washington, D.C. 20402
Preface

The Workshop Proceeding, Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals, was prepared in response to a request from

the Senate Committee on Agriculture, Nutrition, and Forestry that OTA examine

technological opportunities for commercially developing plant extracts. The proceeding describes some opportunities and constraints of commercially developing plant extracts, examples of some work being done in this field, and workshop

participants’ conclusions and recommendations concerning the Government’s role

in the area. Ten technical papers and four overview papers are included in the

proceeding.

Developing new crops or plant products offers a wide range of potential benefits

to the United States and developing countries. Crop diversification and new product development in the United States may substitute domestically produced goods

for petroleum and other imports (including strategic and essential industrial

materials); provide useful new consumer products; increase productive use of land

resources, especially in marginal farming areas; generate employment in areas of

underemployment or unemployment; and provide plant-derived biocides that cause

little long-term ecological damage as alternatives to certain synthetic pesticides.

In developing countries, new crops or new plant-derived products may help stimulate cottage industries, increase local and national self-sufficiency, and perhaps

provide new export industries. This proceeding addresses these opportunities as

well as constraints to and possible impacts of their development.

In regard to protein extraction from tobacco, the proceeding states that the

risk involved in investment in this technology is perceived to be high, and a considerable concern exists that products would have limited marketability because of:

● the health concerns that some attach to tobacco, and

● the changed character of cigarettes and chewing tobacco made from proteinextracted tobacco may not satisfy consumers.

OTA wishes to thank the authors of the workshop papers for their efforts before,

during, and after the workshop, and the following people who reviewed workshop

papers: Alan Atchley, Marvin Bagby, Jack Beal, W. Hugh Bollinger, D.H. Bruhn,

Ernest Bueding, Robert Carney, Geoffrey Cordell, Donald De Jong, Carl Djerassi,

Raymond Doskotch, Richard Edwards, Donald Heynemon, H. T. Huang, Robert

Jacobs, Quentin Jones, Isao Kubo, James Kutney, Julia Morton, David McClintock,

Koji Nakanishi, Guillean Prance, L.H. Princen, Paul Scheuer, Francis Schmitz, David

Seigler, Yuzuru Shimizu, Sarah Sprague, Allan Stoner, and Heber Youngken.

Ill
Workshop Participants

Robert Adams

Manager, Phytochemical Products

Native Plants, Inc.

Salt Lake City, Utah

John Becker

General Manager

Leaf Protein International, Inc.

Raleigh, N.C.

Frederick H. Buttel

Department of Rural Sociology

Cornell University

Ithaca, N.Y.

James A. Duke

Chief, Economic Botany Laboratory

U.S. Department of Agriculture

Beltsville, Md.

Norman R. Farnsworth

College of Pharmacy

University of Illinois

Chicago, III.

William Fenical

Institute of Marine Resources

Scripps Institution of Oceanography

University of California

San Diego, Calif.

Cornelia Butler Flora

Department of Sociology, Anthropology,

and Social Work

Kansas State University

Manhattan, Kans.

Richard R. Harwood

Rodale Research Center

Kutztown, Pa.

Martin Jacobson

Biologically Active Natural Products

Laboratory

U.S. Department of Agriculture

Beltsville, Md.

Pachuab Kwanyuen

Leaf Protein International, Inc.

Raleigh, N.C.

Aklilu Lemma

Senior Scientific Affairs Officer

United Nations Center for Science and

Technology for Development

New York, N.Y.

Frederick L. Mann

College of Agriculture

University of Missouri

Columbia, Mo.

Ara der Marderosian

Philadelphia Colege of Pharmacy and Science

Philadelphia, Pa.

Gordon H. Svoboda

Indianapolis, Ind.

Howard Tankersley

Soil Conservation Service

U.S. Department of Agriculture

Washington, D.C.

Lehel Telek

Science and Education

Agricultural Research Service

U.S. Department of Agriculture

Tropical Agricultural Research Station

Mayaguez, Puerto Rico

E. Richard Wheaton

Science and Education

U.S. Department of Agriculture

Washington, D.C.

Samuel Wildman

Leaf Protein International, Inc. (retired)

Raleigh, N.C.

iv
OTA Workshop Staff on Plants: The Potentials for Extracting Protein,

Medicines, and Other Useful Chemicals

H. David Banta, Assistant Director, OTA

Health and Life Sciences Division

Walter E. Parham, Food and Renewable Resources Program Manager

Susan Braatz, Workshop Director

Phyllis Balan, Administrative Assistant

Nellie Hammond, Secretary

Carolyn Swarm, Secretary

OTA Publishing Staff

John C. Holmes, Publishing Officer

John Bergling Kathie S. Boss Debra M. Datcher Joe Henson

Glenda Lawing Linda A. Leahy Cheryl Manning

v
Contents

Chapter Page

I. Overview of Subject/Issue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

II. Abstracts of Workshop Papers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Tobacco Leaf Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Endodin Combating Schistosomiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Milkweed: A Potential New Crop for the Western United States . . . . . . . . . . . . . . . . . 8

Insect Repellents, Attractants, and Toxicants From

Arid/Semiarid Land Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Commercial Products From Marine Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Anticancer Drugs From the Madagascar Periwinkle . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Strategic and Essential Industrial Materials From Plants . . . . . . . . . . . . . . . . . . . . . . . . 10

Information Useful to Plant-Derived Drug Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

USDA’s Data Base on Minor Economic Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

111. Summary and Discussion of Each Workshop Paper . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Tobacco Leaf Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Crystalline Fraction l Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Fraction 2 Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Green Sludge . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Green Residue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Pigments and Other Bio-Organic Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Low-Molecular Weight Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Protein From Tropical Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Endod in Combating Schistosomiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Milkweed: A Potential New Crop For the Western United States . . . . . . . . . . . . . . . . 24

Insect Repellents, Attractants, and Toxicants from

Arid/Semiarid Land Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Calamus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Big Sagebrush . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Need . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Heliopsis Longipes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Mamey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Basil. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Mexican Marigold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Commercial Products From Marine Marine Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Biomass Conversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Pharmaceutical Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Agricultural Chemicals.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Food and Food Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Enzymes, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Industrial Chemical Feedstocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Needs for Developing Marine Algal Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Anticancer Drugs From the Madagascar Periwinkle . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Strategic and Essential Industrial Materials From Plants . . . . . . . . . . . . . . . . . . . . . . . . 36

Information Useful to Plant-Derived Drug Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

USDA’s Data Base on Minor Economic Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Data ase Files . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Prototype Databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

IV. Findings and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

Opportunities . . . . . . . . .. .. ....... .. .. . .. ... . .... ... ..... 49

Constraints to New Crop Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

vii
Contents-continued

Page

Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

Crop Production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

Industrial Processing . . . . . . . . . . . . . . . . . . . . . . . .. .. .. .. .. ... ... ......O . . . . . . 56

Marketing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

Areas for Possible Congressional Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

Tables

Table No. Page

I. Potential Domestic Crops and Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

2. Information to Reincluded in a ata Base for Drug Development From Plants ....41

3. Data Bases Pertinent to Drug Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

Appendix: Technical Papers

An Alternate Use for Tobacco Agriculture: Proteins for Food Plus a Safer

Smoking Material (Samuel Wildman) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

Leaf Protein Extraction From Tropical Plants (Lehel Telek) . . . . . . . . . . . . . . . . . . . . . . . 78

Chemicals From Arid/Semiarid Land Plants: Whole Plant Use of Milkweeds

(Robert P. Adams). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

Insecticides, Insect Repellents, and Attractants From Arid/SemiaridLand Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

Marine Plants: A Unique and Unexplored Resource (William Fenical) . . . . . . . . . . . . . . . 147

The Role of the Alkaloids of Catharanthus Roseus (L.) G.Don(Vinca Rosea)

and Their Derivatives in Cancer Chemotherapy (Gordon H. Svoboda) . . . . . . . . . . . . . . . 154

Strategic and Essential Industrial Materials From Plants—

Thesis and Uncertainties (Howard C. Tankersley and E. Richard Wheaton) . . . . . . . . . . 170

Information Gathering and Data Bases That Are Pertinent to the Development of

Plant-Derived Drugs (Norman R. Farnsworth and William D. Loub) . . . . . . . . . . . . . . . . . 178

The USDA Economic Botany Laboratory’s Data Base on Minor Economic

Plant Species (James Duke) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196

Ecological Perspectives on the Increasing Use of Plants to

Provide Useful Products (Richard R. Harwood) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215

Potentials for Extracting Protein, Medicines, and Other Useful Chemicals

From Plants: Some Sociological Observations

(A Review of the OTA Workshop Papers) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...221

Plants: The Potentials For Extracting Protein, Medicines, and Other

Useful Chemicals (A Review of the OTA Workshop Papers). .,...... . . . . . . . . . . . . 233

Economic Perspective of Introduction of New Crops (A Review of the OTA Workshop Papers)243
— . —

Overview of Subject/Issue
Overview of Subject/Issue

Historically, plants have served humankind

as sources of foods, medicines, oils, biocides,

waxes, and other useful substances. However,

it was not until the early 19th century that active compounds were isolated in a pure form

from plants, and late in the 19th century that

the chemical structures of natural plant compounds could be determined. A revolution in

chemical technology has occurred in the last

50 years. New technologies have enabled the

isolation, identification, and subsequent synthesis of biological compounds. Although some

chemical compounds found in plants cannot

be synthesized today because of technical or

economic constraints, an increasing number

of chemical compounds are being produced in

the laboratory.

Despite these capabilities, renewed interest

has developed in using naturally produced

chemicals from plants—botanochemicals—as

sources of new food proteins, medicines, biocides, and other materials. The rapid escalation of petroleum prices has encouraged Government and industry to consider plants as renewable sources of botanochemicals that could

reduce the demand for petroleum resources.

Similarly, concern for adequate food supplies,

especially in less developed countries, has

drawn attention to new technologies for extracting high-quality protein from tropical

legumes for livestock feed and human consumption. Better understanding of the ecologically disruptive and persistent effects of some

synthetic biocides has stimulated work on extracting biocidal compounds from plants—e.g.,

insecticides from the neem tree. Because plantderived biocides are biodegradable, they rarely persist for long periods; their impact, although perhaps initially as disruptive to the

ecosystem as a synthetic substance, is temporary.

While only a small proportion of all higher

plants has undergone chemical testing, statistically the probability is high that many unscreened plants contain important substances

for human use. The greatest reservoirs of unscreened plants, however, are in tropical regions, where changes in land use are leading

to the permanent loss of some of these resources before they can be assessed. As a result

of the disappearance of tropical species, there

is a sense of urgency to increase screening efforts and investigate commercial potential of

tropical plant chemicals.

The objective of the OTA exploratory workshop was to provide a basis for general discussion of opportunities, constraints, and potential impacts of new crop and new plant product development rather than to carry out a

comprehensive investigation of potential commercial plant products. The subjects chosen for

discussion, therefore, represent only a small

sample of plant products with commercial potential. An effort was made to include examples of different types of products, including

low cost/large demand and high cost/small demand products; products suitable for development both in the United States and in less

developed countries; and plants that have had

little previous commercial use—namely, arid/

semiarid land plants and marine plants. In addition to papers on specific plant products,

papers on the existing data bases on plantderived drugs and on ecological characteristics

of minor economic plant species were presented. Short summaries of each of the papers

follow.

3
Abstracts of Workshop Papers
Abstracts of Workshop Papers

TOBACCO LEAF PROTEIN

Pilot-scale technology that extracts high-quality protein from young tobacco leaves has been

developed. Soluble proteins extracted from

tobacco plants might be added to foods as nutritional supplements or for functional properties (e.g., gelling, thickening). Although not fully tested, they might have a specialized medicinal use as a pure protein source for kidney

patients. Insoluble proteins might be suitable

as a supplemental livestock feed. The leaf material left after protein extraction might be used

in the manufacture of safer cigarettes with

lower concentrations of toxic substances.

Several important constraints to the development of this technology make its future uncertain. Because a stigma is attached to tobacco

by a large segment of society, there is a strong

likelihood that food products developed from

tobacco would not be readily accepted by the

general public. Tobacco would face strong

competition from alternate sources of protein.

Before this technology could be economically

viable, the residual deproteinized tobacco

would have to be marketed successfully for the

manufacture of smoking products, such as cigarettes. Significant flavor changes and associated characteristics of the deproteinized tobacco may not satisfy consumer tastes. Lastly, expanding the technology from the pilot scale to

commercial scale will require the solution to

certain technical and economic problems.

PROTEIN FROM TROPICAL PLANTS

The leaves of some 500 tropical plants have

been screened by the U.S. Department of Agriculture (USDA) as potential sources of highprotein animal and human foods. Leaf protein

fractionation for livestock feed is based on the

principle that nitrogen-fixing plants contain

higher levels of protein than ruminant animals

can use, and nonruminants can assimilate only

a portion of the total plant protein but cannot

consume the volume of leaves necessary to

meet their protein needs. The high-protein content of these plants allows partial removal of

protein for nonruminant use and subsequent

use of the remainder of the plant and its protein by ruminants. An appropriate combination

of animals for the dual-use of leaf protein

would be hogs and dairy cattle.

The plants with the greatest potential for

commercial LPC (leaf protein concentrate) production are herbaceous nitrogen-fixers. Tropical grasses are naturally too low in nitrogen

to be adequate sources of LPC. Fertilization

with nitrogen increases the protein content, but

the expense of commercial fertilizer is too great

to make LPC production economical. Many

tropical tree leaves contain toxic and antinutritional compounds which limit their use as livestock feed. Processing of the leaves might rid

them of these harmful compounds, but the additional cost and technology requirements to

do so might be prohibitive.

Work on alfalfa in the United States, Europe,

and Japan has demonstrated the potential for

dualwse of plant protein and has provided techniques and machinery that may be adapted to

tropical plants. Although extraction and use of

leaf protein in tropical regions seems promising, especially as livestock feed, a number of

areas need additional research, including extraction methods, energy needs, acceptance of

products, year-round vegetation supply, plant

protein content, plant substances that adversely affect animal and human nutrition, environmental impacts, and cost. The feasibility of

7
8 ● Plants: The Potent/a/s for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

human use of LPC in tropical countries has consumption of high-protein vegetables such

been contested on grounds of health and prac- as collards, mustard greens, amaranths, and

ticality. Especially on small farms, protein the winged bean.

probably can be better supplied through direct

ENDOD IN COMBATING SCHISTOSOMIASIS

The berries of ended (Phytolacca dodecandra), the Ethiopian soapberry plant, after being dried, ground, and mixed with water, are

used in Ethiopia and elsewhere as a detergent

for washing clothes in rivers and streams.

More importantly, within hours the solution

can kill snails that carry schistosomiasis, a

debilitating disease affecting an estimated 200

million to 300 million people and potentially

infecting as many as 400 million others in

many tropical and subtropical countries. The

rapidly spreading disease poses a threat to

large-scale irrigated agriculture and hydroelectric power development schemes in the tropics,

many of which receive partial support from

U.S. development assistance institutions.

A 5-year field study of endod’s effectiveness

against schistosomiasis in Ethiopia showed

that after streams were treated with endod, the

overall prevalence of the disease in 17,000 local

people dropped from an initial 63 to 34 percent.

In children of ages 1 to 6, the incidence of disease dropped from 50 to 7 percent. This and

other tests indicate that ended, in combination

with other drugs to treat already infected people, holds promise for controlling schistosomiasis and other snail-borne diseases.

MILKWEED: A POTENTIAL NEW CROP

FOR THE WESTERN UNITED STATES

Arid/semiarid-land plants already are valuable sources of commercial products, including

candelilla wax, jojoba oil, gum arabic, tragacanth gum, and natural rubber from guayule.

However, many other arid and semiarid land

plants represent largely untapped sources of

chemicals for industrial feedstocks and other

products. For example, pilot-scale research indicates that the showy milkweed (Asclepias

dodecandra) contains many commercially exploitable chemicals. As with many plants, significantly higher value is obtained by fractionation of the plant material into component

parts, any one of which alone would not economically justify milkweed as a crop. The development of milkweed as a commercial crop

is contingent on solving certain agronomic and

processing problems and on the development

of markets for milkweed products.

Dryland agriculture using milkweed and

other potential arid/semiarid crops could be

ecologically and economically beneficial, especially in marginal areas now cultivated with

traditional food and fiber crops. For example,

milkweed might be preferable to existing crops

in the western Great Plains where crop irrigation is causing overuse of the ground water.

Developing new arid and semiarid crops also

might expand agriculture to areas that now

cannot be cultivated with existing crops. Before development of new crops is promoted on

arid/semiarid lands generally considered to be

ecologically fragile, cropping systems and

other agronomic techniques must be available

to minimize ecological disruption,
//.—Abstracts of Workshop Papers • 9

INSECT REPELLANTS, ATTRACTANTS, AND TOXICANTS FROM

ARID/SMIARID LAND PLANTS

Many arid- and semiarid-land plants have

been identified as potential commercial

sources of natural insect attractants, repellents,

and toxicants. Because these plant-derived

chemicals are biodegradable, they might prove

to be preferred alternatives to synthetic chemicals that persist in the environment long after

application. Arid/semiarid plants may be potential new crops on lands that are marginal

or unproductive for traditional food and fiber

crops.

USDA screening has identified seven plants

as particularly promising commercial sources

of natural insecticides, insect repellents, or attractants. These are sweetflag (Acorus calamus), big sagebrush (Artemisia tridentata),

neem (Azadirachta indica), Heliopsis (Heliopsis longipes), mamey apple (Mamea americana), sweet basil (Ocimum basilicum), and

Mexican marigold (Tagetes minuta). Most of

these plants have been used in other countries

for various purposes on a local level but have

not been developed on a large commercial

scale.

Of the seven plants discussed, the neem tree

seems to have the greatest potential as a commercial crop. Although all parts of the tree

repel insects, the seeds are outstanding repellants and feeding deterrents for a wide range

of household and agricultural pests. The rest

of the tree—timber, bark, and leaves—has a variety of economic uses for construction and

medicinal and hygenic applications. The tree

grows well where many other plants present

an erosion hazard or are unproductive, as in

hot, dry climates and on shallow, stony, or

sandy soils. Neem could be encouraged as a

crop to further local economic development,

especially in arid zone countries. Currently,

there are neem plantations in India and in African, Latin American, and Caribbean countries.

USDA has a program to develop neem as a

commercial crop in Puerto Rico and the U.S.

Virgin Islands.

Marine plants have evolved unique biochemical processes and structures in adapting to

their chemical, physical, and biological environments. Although marine plant biochemistry is a relatively new field, research done to

date reveals that marine algae represent potential sources of pharmaceuticals, agricultural

chemicals, foods and food products, industrial

chemical feedstocks, and other useful products.

Despite this potential, little commercial development of marine plant products has occurred

in the United States, with the exception of agar,

carageenan, alginate, and beta-carotene for the

food industry; chemicals for biomedical research; and glycerol for a variety of consumer

products.

The success of tapping the rich potential of

marine plants will depend on greater support

of basic research in marine biochemistry, genetics, nutrition, reproduction, and mass

culturing techniques. However, little Government funding for commercial development of

marine extracts is available, and private sector activities in the field are limited, especially in pharmaceutical development. To ensure

that basic research is translated into commercial application, a close link must be developed

among Government, universities, and industry.

The Sea Grant Program, funded by the Department of Commerce, provides such a link and

demonstrates the effectiveness of such collaboration.
10 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

The isolation, purification, and subsequent

marketing of alkaloids from the Madagascar

periwinkle (Catharanthus roseus) in the late

1950’s and early 1960’s instigated a resurgence

of interest in plants as possible sources of anticancer drugs. Among the many periwinkle alkaloids showing anticancer activity, leurocristine* and vincaleukoblastine* * have reached

the marketplace and are among the most effective cancer chemotherapy treatments available

today. Vincristine, called a “miracle drug”

because it was on the market less than 4 years

after its discovery, shows a 50-percent-complete response rate in children with lymphocytic leukemia when administered alone

and a 90-percent-complete response rate in

combination therapy.

In addition to providing a valuable medicine

for cancer patients, the periwinkle alkaloids

have been very profitable to Ely Lilly, the pharmaceutical firm that developed the drugs. De-

*Known generically as vincristine.

**Known generically as vinblastine,

spite the financial benefits resulting from research on the Madagascar periwinkle, Eli Lilly has shut down its plant screening program.

It was the last U.S. pharmaceutical firm to have

such a program. The U.S. Government has followed suit; the National Cancer Institute’s program to test plants for antitumor activity was

discontinued in 1981. Now that these two research programs have been discontinued, there

are no major initiatives in the United States to

search for anticancer drugs from plants.

The potential of plants as sources of new

antitumor drugs has not been fully explored;

the chemical compositions of only a small portion of the Earth’s higher plant species have

been chemically investigated. Despite the problems and high costs of developing new drugs,

the success of the work on Catharanthus

alkaloids illustrates that new drugs can be

developed from plant resources, and at a profit, The reasons behind the current lack of research on antitumor drugs and the respective

roles of the private and public sectors in such

research should be examined.

The U.S. dependence on imports of essential industrial materials (including “stragetic”

materials essential to national defense) and

petroleum for industrial feedstocks and fuel

could be reduced by domestic production of

plants yielding these substances or their substitutes. In 1979, the United States imported an

estimated $16.5 billion worth of petroleum for

industrial feedstock and $6.5 billion worth of

agriculturally produced industrial materials, of

which some $3.5 billion was for newsprint and

$1 billion was for chemicals extracted from

plants. Domestic production of a portion of

these materials could decrease the Nation’s

dependence on finite petroleum resources and

increase U.S. dependence on agriculturally

produced renewable resources.

Producing these materials in the United

States could benefit farmers and manufacturers

through crop and product diversification. The

Nation could benefit from import substitution,

reduced dependence on other countries for

supplies of strategic and essential materials,

and elimination of the need to stockpile strategic materials. Large-scale domestic production of industrial crops would require reallocation of large areas of land from other uses to

these crops. Assessments of land availability

and the ecologic and social impacts of altering land use should be considered. In addition,

a great deal of research is needed on plant

breeding and agronomy of potential industrial

crops (e.g., guayule, crambe, jojoba, lesquerella,

meadowfoam). Clearly, domestic production of

industrial crops would be economically beneficial, but several social, economic, ecological,

political, and foreign policy implications

should be carefully examined.
Il.—Abstracts of Workshop Papers ● 1 1

Plants play a major role in medicine. Plant--

derived drugs represent approximately 25 percent of total prescriptions dispensed. The retail

value in 1980 of U.S. prescription drugs containing active compounds from higher plants*

is estimated to be at least $8 billion and overthe-counter drugs at some $1 billion. Because

synthesis of almost all of the 50 pure-plant compounds used in prescriptions is not technically or economical feasible now, most of these

compounds still are extracted from plants.

Despite the proven value of plant compounds

as pharmaceutical ingredients, natural product

development virtually has stopped and little

work is being done on tissue-culturing and genetic engineering for production of plantderived drugs. Drug development is relying increasingly on synthesis of new compounds.

The reasons for the disinterest in plant-derived

*Higher plants are those such as conifers and flowering plants,

which possess a well-developed conducting system. Plants such

as mosses, fungi, and algae are not part of this group.

drugs may be lack of an assured plant supply,

feelings that patent protection on natural products is insecure, or a sense that natural products research is unprofitable.

Plant drug development entails many steps,

including plant selection and collection,

bioassay procedures, isolation and identification of biologically active plant compounds,

and clinical evaluation and marketing. Any

shortcuts to systematize plant selection for

screening and select appropriate bioassay procedures would decrease research time and expense and increase the chances of discovering

marketable chemicals. Ten automated data

bases that provide data on plant sciences, agriculture, and the chemistry and pharmacology

of natural products can be used as screening

aids for plant extracts work. One of these data

bases, NAPRALERT, consisting of computerized files of research findings and published

folklore information relevant to plant-derived

drugs, can be extremely valuable to research

on plant-derived drugs.

Large numbers of plant species exist with

commercial potential that remain undeveloped

as crops. There is an overwhelming number

of climatic, ecological, and anthropological

variables associated with these plants. Since

1971, the USDA Economic Botany Laboratory

has been developing a computerized information system on minor economic plant species.

The system’s files include information on

agronomy, agroforestry, ecology, ethnomedicine, nutrition, pathology, and uses of several

hundred plants. There is also a climate file with

data for over 20,000 locations worldwide. A

wide variety of questions can be answered by

linking these files through a computer. For example, the system can help match new crops

with environments in which they would be

most successful, identify potential multipurpose crops for certain locations, determine the

yield and nutritional value of a particular plant

under given ecologic and agronomic conditions, help determine the potential spread of

an introduced weed or pest, and identify

sources of plants or specific germ plasm useful

for crop improvement. These files are now offline because of lack of funding. If maintained

on-line and developed further, the system could

be a valuable tool for new crop- and plantproduct development.
Ill.

Summary and Discussion

of Each Workshop Paper
III ●

Summary and Discussion

of Each Workshop Paper — — —

TOBACCO LEAF PROTEIN

The concept of using leaf protein as a food

is not new. Over the last 60 years, scientists

from several countries have researched the extractability of proteins from leaves and preparation of leaf protein concentrate (LPC). The

greatest impetus for leaf protein research came

in the early 1940’s when Norman Pirie of England examined the potential of producing LPC

as a source of protein for human consumption

to alleviate wartime food shortages. After

World War II the interest in leaf proteins for

human use waned because their green color

and slightly grassy taste hindered consumer acceptance of them as human foods. Since that

time, the Pirie process for leaf protein extraction has been modified for commercial production of LPC for livestock feed. Recently, a new

technique has been developed and tested at the

pilot-plant stage that can extract a high-quality,

purified protein from immature tobacco plants.

It has been proposed that tobacco be used as

a dual- or multi-product crop for proteins and

smoking and chewing tobacco,

The extraction process yields six products.

They are:

Crystalline Fraction 1 Protein

Fraction 1 protein is a water-soluble, tasteless, and odorless white powder. It is nutritious; when fed to rats, crystalline Fraction 1

protein exhibited a higher protein efficiency

ratio (PER) than casein, the common standard

for comparing the nutritional quality of proteins. Because it is tasteless and odorless, Fraction 1 protein can be added to foods to improve

their protein content and quality without

changing their taste or smell. This product can

be added to foods for its albumin-like functional properties such as heat set and gelling.

It has been suggested that if crystalline Fraction 1 is washed free of sodium and potassium,

it might be useful for kidney patients as a

source of high-quality protein, although this has

not been substantiated by research.

Fraction 2 Protein

This product also is water-soluble and nutritious and might be used as a protein supplement for food products such as cereals. Its

functional properties are not so desirable as

those of Fraction 1 protein, however.

Green Sludge

Green sludge consists of water-insoluble proteins and starch. It possibly could be marketed

as a feed for poultry and other nonruminant

animals. Green sludge can be converted by solvent extraction to a material similar to soybean

meal in properties and amino acid composition.

Green Residue

This product represents the fibrous material

left after protein extraction. The solids are composed of more than 50 percent cellulose and

hemicellulose and about 13 percent protein. It

is similar to alfalfa hay in nutritional value, The

green residue can be converted through organic solvent extraction to white fibers suitable for

cigarette manufacturing. The resultant deproteinized cigarettes would be lower in tar and

nicotine than commercial cigarettes today.

Pigments and Other

Bio-Organic Compounds

Organic solvent extraction of the green residue and green sludge produces pigments and

other organic compounds. Carotenoids can be

15
16 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

separated out and possibly marketed as poultry

feed supplements.

Low-MoIecular Weight Compounds

This product, composed of water-soluble

sugars, amino acids, vitamins, salts, and other

compounds, might be used as a fermentation

liquor after it is concentrated by evaporation.

The extraction procedure for tobacco protein

is fairly simple. First, the aboveground portions

of the tobacco plants are crushed. The liquid is pressed out, leaving behind the solids

(green residue). The green juice is heated rapidly to 1250 F (520 C) then quickly cooled to room

temperature, causing green particulate matter

(green sludge) to settle out of the now brown

liquid. The brown juice is pumped to a storage

tank where within 6 to 10 hours Fraction 1 protein crystallizes out of solution. The crystals

are collected and washed. The remaining liquid

is acidified, causing Fraction 2 proteins to

precipitate out of solution. They, too, are collected and washed.

The process has the following advantages:

providing a high-quality protein from a plant

already grown on a total of 2.5 million hectares

over a wide geographical range, and providing

a smoking product that is lower in the constituents believed to be health hazards. Although

the results of pilot-scale research seem promising, several technical, economic, social, and

environmental problems would have to be

solved before tobacco protein extraction could

be viable on a commercial scale.

This procedure was developed by Leaf Protein, Inc. (LPI), a small venture capital corporation. To investigate the potential of this process on a commercial scale, LPI formed a joint

venture with the North Carolina Farm Bureau

Federation. The Federation, together with General Foods Corp., helped finance a pilot plant

in the tobacco growing region of North Carolina, a small plant able to process about a ton

of fresh plants every 9 to 10 hours. The plant

was operated first in August 1980. Each experiment required a minimum of 600 lbs of fresh

plants. Climatic and technical problems were

encountered, and it was not until July 1982 that

the pilot plant was consistently able to produce

Fraction 1 protein of high purity. Although the

pilot-scale operations appeared promising, at

the end of the tobacco growing season the research facility was closed and the equipment

was sent to the University of Florida which is

using it experimentally to produce pig feed.

The research was discontinued because of lack

of industry interest in investing in commercial

scale-up of the LPI process. This lack of interest

was not caused by predicted scaling-up problems but by fears that the products would have

limited marketability because of the social

stigma attached to tobacco and the changed

character of cigarettes and chewing tobacco

would not gain consumer acceptance. The risk

involved in investment was perceived to be too

high.

Consumer attitude is perhaps the most serious deterrent to using tobacco as a source for

protein. Given tobacco’s negative image in the

eyes of many American consumers, the appeal

for foods containing tobacco leaf protein could

be questionable. Tobacco protein would have

to compete with the already abundant sources

of protein in the United States—ranging from

vegetable oilseed proteins to animal proteins—which are well-established and probably

more readily acceptable to the public. The

potential retail value of the extracted protein

alone would not economically justify growing

tobacco since all three proteins together account for only about 20 percent of the total

estimated value of the finished products from

tobacco. As much as 55 percent of the crop’s

estimated value would come from sale of the

fibrous portion for cigarette manufacture.

Unless the deproteinized fiber is acceptable to

manufacturers and consumers, the process

would not be profitable. No commercial firm

has been willing to invest in commercial scaling-up of the LPI system. Whether the changed

character of a cigarette would appeal to consumer taste is in question but will be a major

factor in the economic success of tobacco protein extraction.

There are many technical constraints facing

the LPI process, both at the agronomic and the
Ill.—Summary and Discussion of Each Workshop Paper ● 17

processing level. The time at which the tobacco is harvested is critical because the leaf protein is surprisingly variable on a daily basis.

Because the proteins and other leaf constituents deteriorate rapidly after harvesting, the

harvested material must be processed almost

immediately. At the processing level, the leaf

pulp is difficult to work with when using conventional conveying machinery because it is

viscous and is corrosive to metal. Another

problem which is not so apparent at the pilot

level as on the commercial level is disposal of

wastes. Since about 90 percent of the plant material is water, handling and disposal of large

amounts of fluid must be arranged. The brown

juice left after extraction of the proteins and

fiber has a high biological oxygen demand

(BOD) so would be a source of pollution if released unaltered into an aquatic system. Evaporation processes to condense the liquids, however, are expensive. Solvent recovery is another

problem. Because they are expensive, a certain

proportion of the solvents used in processing

green residue and green sludge must be recovered. This may be a problem encountered with

commercial scale-up.

The environmental impacts of tobacco as a

crop should be examined. Tobacco needs large

inputs of energy, biocides (insecticides, herbicides, fungicides, nematicides), and fertilizers

for cultivation. When grown in the conventional manner, tobacco is “hard on the soil. ”

It readily extracts soil nutrients, particularly

nitrogen, so unless large amounts of fertilizer

are applied to tobacco fields, the crops over

time will tend to decrease soil fertility. When

grown for protein extraction, tobacco plants

could be harvested four times per growing season. This faster rotation probably would lead

to even faster nutrient depletion and would require greater fertilizer inputs than even conventional tobacco crops. Cultivation of tobacco, an annual planted at relatively wide spacing, presents an erosion hazard. The denser

spacing used for protein tobacco compared

with conventional tobacco might help reduce

erosion rates. However, more frequent harvests, repeatedly exposing the soil to wind and

rainfall, probably would increase erosion.

Conventional tobacco production requires

large inputs of biocides. Pesticide inputs may

decrease because the “cosmetic” appearance

required of the cigarette tobacco leaf is not

necessary for protein extraction. Seedlings

either would be raised in seedbeds that have

been fumigated to kill micro-organisms and

then transplanted in the field or would be

raised directly in newly cleared land. The latter obviously is not desirable or possible in

many places. The need for herbicide application would be greater if tobacco were grown

for protein extraction because repeated harvests provide increased opportunity for weed

encroachment. It seems that growing tobacco

for protein extraction would be equally, if not

more, ecologically disruptive than conventional tobacco, a crop widely recognized as a

resource-demanding crop.

A great deal more economic information is

needed to assess the commercial viability of the

process. No processing costs at the pilot level

or projected commercial processing costs are

available. In addition, the ability of the products to enter the marketplace must be assessed.

The products would have to be able to compete on the market with alternative products

in price, availability, ease of use, and consumer

taste preference (with products for human consumption). For example, Fraction 1 protein

would have to compete with egg albumin as

a functional food additive and the bio-organic

compounds from the green residence and

green sludge with alfalfa as a source of carotenoids for poultry feed. Both egg-whites and

alfalfa are well-established in these markets and

tobacco might have difficulty attracting a portion of these markets away from them. Most

important, the deproteinized tobacco fibers

would have to be able to compete with mature,

cured tobacco leaves. Not only would a different taste have to be acceptable to the consumer, but the processor would have to be willing to make processing changes for the new

product, An important factor in market entrance is the amount of product available. If

only limited quantities of a product in a largevolume market (e.g., fibers for tobacco or for

livestock feed) are available, industry may be
18 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

unwilling to go to the trouble and expense of

using small and/or intermittent amounts of the

products.

Although the LPI process appears promising

at the pilot-level scale, a great number of

technical, ecological, social, and economic barriers stand in the way of commercial feasibility. The cost of taking this process from the pilot-plant scale to commerical production scale

could be high. Although the pilot-plant operation was supported by private capital, the private sector is showing reluctance to work with

a tobacco-related product. Despite potential advantages of the products, financial backing for

further research on agronomic, extraction,

and product testing and marketing has not

been forthcoming. It seems that tobacco processors are not interested in altering an already

profitable manufacturing system to incorporate

processing of tobacco proteins of uncertain

marketability, and that the food industry is unwilling to invest in a crop carrying such a social stigma. In addition, tobacco proteins have

not undergone mandatory Food and Drug Administration (FDA) testing on animals to assess

their safety for human consumption. Until this

happens food processors may be leery of the

possible presence of toxic compounds in the

proteins.

There is some evidence that the protein extraction process might be used successfully on

soybeans, clover, alfalfa, tomato, spinach, and

other crops which are less ecologically disruptive and more socially acceptable. These plants

would face many of the same problems with

research and commercial scale-up that tobacco faces, but could be more acceptable to producers and consumers. Perhaps further research should investigate these alternative

crops for LPI processing.

PROTEIN FROM TROPICAL PLANTS

At the present growth rate, world population

will double within the next 30 to 40 years. This

population increase will be most rapid in the

less developed countries of the humid lowland

Tropics, where annual increase in food production remains low. LPC extracted from tropical

plants is being investigated as a possible source

of protein. LPC is prepared from alfalfa on a

large commercial scale in Europe and the

United States. Because alfalfa has not been

grown successfully in the humid Tropics, suitable tropical replacements are needed for leaf

protein extraction.

Leaf protein fractionation is based on the

principle that nitrogen-fixing plants contain

higher levels of protein than can be used by

ruminant animals and that nonruminants, able

to assimilate only a portion of total plant protein, cannot consume the volume of leaves necessary to meet their protein needs. The high

protein content of these plants allows for partial removal of protein for nonruminant use

and subsequent use of the remainder of the

plant by ruminants.

USDA’s Tropical Agriculture Research Station in Mayaguez, Puerto Rico, has tested at

least 500 introductions of tropical plants as possible sources of LPC. Desirable characteristics

of plants as sources of leaf protein concentrate

include high protein content, high dry-matter

content, readily extractable protein from freshly cut plants, good regrowth potential, ability

to fix nitrogen, erect growth for easy mechanical harvesting, nontoxicity, and low concentration of antinutritional substances.

The extraction procedure used was a relatively simple process in which the liquid

pressed out of the leaves was subjected to successively higher temperatures, thus causing the

proteins to precipitate out of solution. At 55°

C, a green coagulum formed and was separated

by centrifugation, washed several times, and

spread in thin layers on glass plates to dry. The

supernatant from the centrifugation was

heated carefully to 640° C. The white curd coagulum that formed was separated by centrifugation, washed with acetone, and dried in a rotary evaporator. The liquid was heated further
Ill.—Summary and Discussion of Each Workshop Paper ● 19

to 820 C. After cooling, a light tan precipitate

formed and was processed in the same way as

the 64° C fraction.

The spontaneous coagulation of protein in

the juice extracted from some plants (subsequently called Type I plants), including cassava

(Manihot esculenta), leucaena (Leucaena

leucocephala), and many other tree legumes,

was observed during the survey of tropical

plants. Another group of plants (Type II)

yielded a green protein coagulum after the extracted green plant juice was heated to 55° C

and yielded a very small quantity of a light tan

precipitate at 820 C. This first was observed

with leaf protein extract of sorghum-sudan

grass hybrids and other grasses. Careful heat

fractionation of aqueous leaf extracts of other

plants (Type III) yielded three distinct protein

fractions: a greencoagulumat550 C, a copious

white protein precipitate at640 C, and a small

amount of light tan precipitate at 820 C. These

are the most promising plants for leaf protein

extraction; species selected for further study

were chosen from this group. A final group

(Type IV) includes plants in which the proteins

in the aqueous extracts do not precipitate either

spontaneously or after heat treatment.

Leaf protein concentrates subsequently were

prepared from seven Type III plants (Vigna

unguiculata, Clitoria ternatea, Desmodium distortum, Psophocarpus tetragonolobus, Macroptilium lathyroides, Phaseolus calcaratus, Brassica napus) and leucaena and cassava, both

Type I plants. The protein quality of the LPC

extracted from these plants was evaluated

using rats. The tropical legumes cowpea (Vigna unguiculate), Desmodium distortum, rice

bean (Phaseolus calcaratus), and winged bean

(Psophocarpus tetragonolobus) gave excellent

results, comparable to those obtainable from

alfalfa LPC. The LPC from these plants had

amino acid contents similar to each other and

to reported values for alfalfa LPC and soybean

meal. The tests supported the suspicion that

the spontaneously precipitated protein concentrate from Type I plants would have less nutritional value; rats fed LPC from cassava and leucaena grew poorly. USDA investigations indicated that with current methods, good quality

leaf protein concentrates for nonruminants

could not be prepared from many of the leguminous tree leaves because the presence of

phenolic substances negatively affects the

nutritional value of the extracted proteins. The

leaves of some of these species, however, could

be used as feed for ruminants.

Investigations of tropical grasses as sources

for leaf protein extraction showed them to be

low in extractable protein. Nitrogen fertilizer

could be applied to fields to increase the protein content in grasses, but the increased value

probably would not offset the cost of the fertilizer. Tropical grasses were considered poor

sources of LPC because they have higher production and processing costs and lower quality and quantity of extractionable proteins.

The following conclusions were drawn from

this relatively short investigation of possible

tropical plant sources for leaf protein extraction:

●

●

●

●

Some tropical plants are sources of LPC

that are equivalent to alfalfa LPC in yield,

extractability, and nutritional quality.

A single crop in the Tropics cannot be

used for year-round production; a pattern

of different plants has to be formulated for

rainy and dry seasons.

Cassava, leucaena, other tropical trees,

and tropical grasses seem to be unpromising as potential sources of LPC.

The type and number of protein fractions

obtained by heat fractionation can be used

as a rapid preliminary method to screen

plants for protein extraction potential.

Machinery has been developed in England

and the United States for LPC processing.

Some are used for large-scale commercial LPC

operations in Europe and the United States,

and others have been used to assess its viability for on-farm and village-level LPC production. Research on village-level LPC production

has been carried out in India, Pakistan, and Sri

Lanka. Work in Aurangabad, India, is the most

relevant to practical application of the LPC production systems on the village level. Establishment of a commercially viable, locally operated

LPC production unit at a village farm was at-
20 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

tempted. The green protein concentrate from

alfalfa was used as a milk replacement for

calves (thus making the cow milk available for

human consumption), as poultry feed, and as

human food. The pressed crop was fed immediately to cows. The cost of equipment and a

dairy unit of five to six cows was assessed at

$4,450, which is prohibitively expensive for a

small-farm operator but probably affordable for

village cooperatives. Concurrent research in

India on LPC production concluded that on a

nutritional basis, leaf protein would be much

less expensive than most protein from grain

legumes consumed in the area and that a LPCcontaining product made for human consumption could provide half the daily protein requirements of a child at a price affordable to

the majority of Indian poor ($0.025 to $0.03 per

day).

On-farm leaf protein fractionation has been

researched in Britain, Australia, and the United

States. The on-farm system is that after harvesting, the crop is processed to produce pressed

forage for ruminants and a juice with soluble

proteins for nonruminants. Processing takes

place on a farm and at least one of the products

is used at the production site. The ideal situation would be a combined dairy and hog farm

where the crop is grown and extraction products used onsite, thus reducing transportation

expenses, storage costs, and spoilage. Research

at the University of Wisconsin at Madison has

concentrated on development of a weather-independent, on-farm forage-harvesting system

using a protein fractionation process. After

harvesting, the main produce is pressed forage

that can be preserved directly as silage. Field

losses from harvesting and baling are reduced

and a higher percentage of the protein content

can be retained in pressed residue than in sundried hays. Research results indicate that ruminants respond to being fed pressed residue

as they do nonfractionated plants. The juice extracted from the plant material could be fed

directly to hogs to minimize storage and preservation expenses. The proteins in the juice

degrade rapidly and the carbohydrates ferment

within a day, so the processing must be geared

to the feeding time of the animals. Proteins

could be isolated from the juice by fermentation, but the product is not acceptable yet to

hogs.

Commercial LPC production was initiated in

1967 at the USDA Western Regional Research

Center in Berkeley, Calif. A highly mechanized

process, the Pro-Xan process, was developed

for obtaining LPC from alfalfa. The first commercial application of this process took place

in France in association with a commercial alfalfa dehydrators plant. (Dehydration is carried

out immediately after harvesting to avoid losses

from haymaking and ensiling and to produce

a product higher in protein content than hay

or silage.) Leaf protein concentrate from alfalfa now is prepared on a large commercial scale

in Europe and the United States for livestock

feed. There are plans to open a plant in New

Zealand, and two pilot plants have been set up

in Japan.

Attempts to process LPC to obtain an acceptable good-grade product have been unsuccessful. Green LPC from the 550 C fraction can be

produced economically, but its green color,

grassy flavor, and low volubility have prevented acceptance by consumers and food producers. Purifying this protein concentrate by

solvent extraction is technically feasible but

costly and only partially effective. The white

protein fractions separated at 64° and 820 C

are nutritious but are practically insoluble. If

soluble, they would be of greater use to the food

industry. Producing a water-soluble, blandtasting white protein using various filtration

techniques including diafiltration, ultrafiltration, and gel filtration has been attempted.

Although gel filtration seems to be the most effective system, it is very expensive. Another

method has been developed that produces a

pure, water-soluble protein at a lower price

than gel filtration. This is a crystallization process used to extract Fraction 1 protein from

tobacco. * Although this process seems to be

technically feasible at the pilot-plant level, its

economic feasibility has not been proven and

has encountered constraints to commercial

scale-up.

*See paper by Wildman in the appendix.
Ill.—Summary and Discussion of Each Workshop Paper ● 21

Use of LPC technology in developing countries is most promising as applied to mediumsized production systems such as cooperatives,

organized communities, and large farms. Onfarm production of LPC is too expensive and

labor-intensive to be feasible for most farmers

who own or lease small plots of agricultural

land. The system is probably most adaptable

to cooperative farming operations, such as a

combined dairy-hog operation. Onsite use of

the products offers many advantages including

lower transportation and storage costs, reduced waste because leaf production can be coordinated with demand for LPC and pressed fodder, and ability to use excess pressed juice for

irrigation water.

Large-scale LPC production might be possible in developing countries if incorporated into

an integrated production system, such as an

operation combining dairy or beef cattle with

hogs or poultry. The high degree of coordination and planning of such an enterprise probably would restrict it to public ownership or

to capital- and management-intensive private

firms, such as beef exporters. While this would

benefit foreign exchange earnings, it would fail

to provide an inexpensive, efficient protein

source for those in developing countries who

need it most.

Screening of tropical plants for extractable

protein has produced several good candidates

for LPC production in tropical and subtropical

countries. Processing machinery has been developed for alfalfa LPC production, but it might

be adapted for use on tropical plants to meet

developing country needs. Before LPC production using tropical plants is feasible, however,

comprehensive studies should be conducted on

agronomic of plants chosen for protein extraction, economic feasibility, farmers’ acceptance

of LPC extraction and use, and production

technologies. A variety of agricultural, economic, and social factors and impacts must also be

considered.

ENDOD IN COMBATING SCHISTOSOMIASIS

Rural people in Ethiopia and certain other

countries traditionally have washed their

clothes with a detergent solution made from

dried and ground ended berries. Ended (Phytolacca dodecandra), the soapberry plant, is a

shrub that is closely related to the American

pokeweed plant. In 1964, researchers studying

the distribution of disease-carrying snails in

streams found large numbers of dead snails immediately downstream from people washing

clothes using ended as a detergent. Subsequent

phytochemical studies indicated that ended

contains effective biocidal compounds. Ended

is being studied as a potential molluscicide for

use against snails that carry schistosomiasis.

Schistosomiasis is a debilitating snail-borne

disease common throughout the Tropics and

subtropics. It is one of the most serious and

rapidly spreading parasitic diseases of humankind, affecting an estimated 200 million to 300

million people and potentially infecting an additional 400 million. The disease is spread

when uninfected people work and bathe in the

same water as infected people. New shallowwater habitats for snails, the intermediate

hosts, have been created by irrigation, hydroelectric power, and other water-related projects, many of which have been funded by international agencies.

No single method to control schistosomiasis

effectively has been found. Ideally the most effective treatment for the disease is site-specific

and repeated molluscicide applications combined with mass treatment of all infected people, improved environmental sanitation, and

health education. However, no safe, effective,

and affordable drug suitable for mass treatment

has been found, and available molluscicides are

inadequate or expensive. Environmental sanitation and health education are long-range

measures. For now the most practical and effective method to control schistosomiasis is

through a combination of selective treatment

of infected individuals and control of new
22 ● Plants: The potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

transmission by killing the host snails at each

proven site of infection.

Although several chemical molluscicides

have been used within the last few decades to

control schistosomiasis and other snail-borne

diseases (e.g., copper sulphate, Frescon, sodium pentachlorophenate, Yurimin), several of

them are no longer produced either because

they are ineffective or cannot be marketed. The

only molluscicide recommended by the World

Health Organization is Bayluscide, an expensive chemical used only in a few developing

countries with the help of external financial

assistance. The lack of a market as a result of

developing countries’ limited foreign exchange

has discouraged the private sector from developing other molluscicides. The discovery of endod and the lack of adequate and affordable

chemical molluscicides have stimulated the

testing of plants as potential molluscicides.

Croton (Croton tiglium, C. macrostachys), ambrosia (Ambrosia maratima), and jatropha

Jatropha curcas) show some promising molluscicidal activity, but a great deal more work

must be done to evaluate their potential as commercial molluscicides. As recognized by a

workshop on plant molluscicides convened by

the United Nations Development Programme,

World Bank, and World Health Organization

in January 1983, ended seems to be the most

promising plant molluscicide evaluated to date.

whereas several other chemical molluscicides

are unstable in intense sunlight or under different water pHs and concentrations of organic

or inorganic matter in the water, ended remains stable in sunlight and under a wide

range of water conditions. It is a potent molluscicide, killing snails within hours. Tests

showed ended to have no mutagenic properties, indicating that widespread use of it as a

molluscicide might not pose a safety hazard to

humans.

A 5-year pilot study investigating the effect

of ended on schistosomiasis was carried out

in northern Ethiopia between 1969 and 1974.

Systematic application of locally collected endod berries over the 5 years reduced the prevalence of schistosomiasis in children aged 1 to

6 from 50 to 7 percent, and in the entire population (17,000) from 63 to 34 percent. The incidence of disease in an untreated nearby village

was almost constant over the course of the

study, indicating that the reduction in the

treated village was as a result of ended applications. The cost of the treatment amounted to

only US $0.10 per person per year. A critical

element in the success of this control study was

local political support and community participation. The local political officials and municipal council were involved in the planning and

execution of the study, and the council provided finances, manpower, and facilities.

In addition to its value as a molluscicide, the

ended berry may have commercial potential as

a detergent; an insecticide for the control of

mosquitoes, the black fly that carries river

blindness, and other water-breeding insects; a

fungicide against certain human skin diseases;

a spermaticide or an abortifacient. Ended berries have been used in Ethiopia and many other

tropical countries for centuries to control an

aquatic leach that is a major pest of livestock.

The berries are also effective against snails that

spread fascioliasis, a serious cattle and sheep

disease.

Most chemical studies done on ended to date

have focused on saponins, the biocidal compounds in the berries. Saponins account for

only 25 percent of the dry weight of ended berries, and the berries in turn represent only a

small proportion of the total plant biomass. The

berries, leaves, stems, and roots could be potential sources of other useful products including

pectins, thickening agents, starches, sugars, animal feed, and fuels. As research on ended

progresses, these and other uses for the byproducts might be developed. Ended is a potential

multipurpose crop that could provide products

for local use or support local industries.

The active chemical in ended berries has

been isolated, identified, and named Lemmatoxin. Three extraction procedures have

been developed, two of which are based on solvent extraction and the third on fermentation.

The fermentation method is simple; berries are

ground, soaked in water, and left in a warm

place to ferment by means of the yeast cells
III.—Summary and Discussion of Each Workshop Paper . 23

normally found on ended berries. This is perhaps the most practical extraction method for

developing countries to use. Processing equipment is affordable, it can be supplied and

operated locally, and no extraction solvents

have to be imported. The fermentation extract

can be applied in a variety of ways. It can be

dusted on the surface of the water as a powder,

sprayed on the water as an emulsion, or compressed into briquettes to allow for slow release

of the active chemical.

If high-potency ended varieties could be

grown locally, the dried and ground berries

could be applied directly to rivers, streams, and

irrigation channels. This would avoid the processing costs involved in preparing an extract.

A study carried out between 1976 and 1981

tested 65 different strains of ended and chose

three on the basis of molluscicidal potency,

berry yields, and resistance to insect pests and

drought. These three strains subsequently were

used in cloning experiments using tissue culture. Plantlets developed through mass propagation have been distributed to Brazil and three

African countries for field trials. Additional

research is using tissue-culturing for in vitro

biosynthesis of the active molluscicidal principle.

Although research on chemistry, extraction

application, and toxicity of ended has progressed rapidly since 1964, a great deal more

toxicological, agronomic, and economic research is necessary before large-scale application of ended for control of schistosomiasis and

other snail-borne diseases could be possible.

Toxicity studies on sheep and dogs showed

that while intravenous injection of ended can

be fatal, oral intake of small to moderate

amounts can be tolerated by animals and large

amounts induce vomiting. This emetic property acts to protect people and animals from possible overdoses. Ended berries, leaves, and

roots have been taken orally for centuries in

several African countries for various medical

purposes, including birth control and ridding

the body of internal parasites. Had ended

shown negative effects, it probably would have

been discarded long ago. Mutagenic tests on

ended berries carried out in vitro have been

negative. However, more comprehensive mutagenic and toxicity tests should be carried out

on a variety of different animal species to provide more complete evidence of ended’s safety.

Because ended has never been grown commercially on a large scale, it will have to be subjected to a range of agronomic studies. Agronomic research on ended during the last decade has concentrated on selection and breeding

of plants for good growth and berry productivity and potency. Some studies have recently been carried out in Ethiopia on its plant ecology and susceptibility to pests, particularly to

a stem-boring fly that kills young shoots. Data

have also been collected on plant nutrition, germination, spacing, and irrigation. This preliminary work will have to be expanded; field trials

are needed to determine both the agronomic

needs of ended and the ecological effects of

cultivating the plant, including impacts on soil,

water availability, and pest outbreaks.

Although no comprehensive ecological studies to determine the effects of ended application on streams have been conducted, observations indicate that local animal populations

are largely unaffected. Any localized effects of

ended application are unlikely to be long-lasting because the active chemical biodegrades

rapidly. Within 24 to 48 hours ended’s potency declines. Extensive research is needed to

provide comprehensive data on ecological impacts.

In summary, ended appears to be a promising potential as a molluscicide for controlling

schistosomiasis. Research on endod, however,

is still at an early stage. Before ended can be

used as a molluscicide, far more research is

needed on its toxicity, agronomy, ecology, economics, extraction, and application techniques,

cost effectiveness compared to other molluscicides, and the distribution and marketing of

berries or the extracted molluscicide. In addition, its potential as a multiproduct crop should

be examined.

Ended could be a community-controlled solution in developing countries to the widespread problem of schistosomiasis. Because the

plant can be grown locally and the biocidal
24 . P/ants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

compound extracted simply using a low-technology fermentation method, inexpensive local

production of the molluscicide is possible. The

alternative of importing expensive Bayluscide

or another chemical molluscicide is not a viable

option for most developing countries with limited foreign exchange. Ended could be cultivated and extracted either publicly or privately and then applied to infection sites by the

community. The public sector would have to

bear the startup research costs for such a

community-based public health project, but financial assistance might be sought from development assistance agencies such as the U.S.

Agency for International Development. Once

started, a project could be sustained by local

revenues and paid or volunteer community

labor.

Ended use need not be restricted to schistosomiasis control in developing countries. Further research may develop endod’s potential

as a source of larvicides, insecticides, spermatocides, or other products. A similar community-based project based on the use of ended

as a larvicide for the control of malaria perhaps

is another future application. Ended might also

be investigated as a biocide for pest control in

the United States.

MILKWEED: A POTENTIAL NEW CROP

FOR THE WESTERN UNITED STATES

Arid/semiarid-land plants in the United

States represent relatively untapped sources of

valuable oils, waxes, natural rubbers, insecticides, medicines, and important chemical

feedstocks. These chemicals, produced by

plants as defenses against predators, pests, and

climatic stresses such as temperature extremes

and drought, could be extracted to provide a

variety of commercial products. Interest in

arid/semiarid-land plants as sources of insect

repellents, attractants, and toxicants; * fossil

fuel substitutes; and chemical feedstocks** is

growing. The showy milkweed (Asclepias

speciosa), discussed in greater detail later, is

an example of an arid/semiarid-land plant

being investigated as a potential multipurpose

crop for chemical feedstocks and fiber products. Arid and semiarid lands, often considered

agriculturally unproductive in relation to traditional U.S. food and fiber crops, could become

important for the production of a variety of

commercial chemical extracts.

Despite the general lack of attention to the

commercial potential of arid/semiarid-land

plants, some of these plants already provide a

variety of commercial products. Some arid/

*See paper by Jacobson in the appendix.

**See paper by Tankersley and Wheaton in the appendix.

semiarid-land-plant extracts used in the United

States are jojoba oil, gum arabic, tragacanth

gum, candelilla wax, and natural rubber from

guayule. Jojoba oil is a valuable lubricant able

to withstand high temperatures. The first commercial harvest of cultivated jojoba plants in

the Southwest United States occurred in 1982;

until then only wild plants had been harvested.

The market value of imports of gum arabic,

used in the food industry for its functional

properties, was about $8 million in 1982. Gum

arabic is obtained from an Acacia species

native to Africa and the Middle East, but a related species could be grown in the United

States to supply an equivalent gum and provide

savings in foreign exchange. Tragacanth gum

is used in pharmaceuticals and cosmetics and

as a thickening agent in some prepared foods.

Although the plant could be grown in the

United States, gum is imported from Iran. As

a result of political instability in the area, imports recently have been erratic. The United

States has had similar problems with procuring candelilla wax which is imported from

Mexico. Imports dropped by over 50 percent

between 1978 and 1982 as a result of harvesting problems. Guayule, a desert shrub that contains natural rubber, could be grown in the

United States to provide a substitute for Hevea
Ill.—Summary and Discussion of Each Workshop Paper ● 25

rubber imported from Southeast Asia. During

World War II when the supply of imported rubber was cut off, guayule was produced in the

Southwestern United States as an alternative

source of natural rubber. Production was discontinued after the war when synthetic rubber became available and importation of natural rubber resumed. Interest in domestic production of guayule has again arisen with increasing demand for rubber and higher prices

for hydrocarbons and petroleum-based industrial feedstocks. Semicommercial production

is being carried out in the Southwest United

States. *

A major constraint to developing new arid/

semiarid-land plants and plant products is lack

of adequate field-screening procedures. The

availability of good field-screening technologies

could help identify promising species for research and locate good sources of germ plasm

(e.g., for high oil content, high biomass productivity) for potential and existing crops. Chemical screening generally has been done in the

laboratory by solvent extraction. Fairly recently, two laboratory techniques, wide-line nuclear magnetic resonance (NMR) and near-infrared reflectance (NIR), have been developed for

more rapid screening, All three methods require that plants be brought in from the field

for laboratory analysis. Solvent extraction must

be done in the laboratory; NMR is not portable

enough for field screening; and even though

portable NIR units are available, plant material

still has to be brought to the lab. Collecting,

preparing, and documenting field samples are

time-consuming activities, and because most

of the material will be unpromising and therefore discarded, they are not cost effective. The

plants yielding good laboratory results have to

be relocated in the field, a task that is often difficult. It would be far more time- and cost-efficient if plants could be screened rapidly in the

field and seeds or cuttings from the promising

plants collected then. Lack of adequate fieldscreening techniques poses a serious deterrent

*See OTA background paper entitled Water-Related Technologies for Sustainable Agriculture in Arid/Semiarid Lands:

Selected Foreign Experience, ch. V, for more information on

guayule.

to the search for potential new crops and plant

products.

A plant should be screened for a range of

chemical compounds to investigate its potential as a multiproduct crop. Once the plant material has been collected and transported to the

processing site, additional costs for extracting

more than one product may be relatively small

but can add significantly to the total commercial value of the plant. Multiple-product development can justify the costs of growing, harvesting, and transporting the crop and extracting the chemicals. In addition, the development

of many products helps buffer the market risk

of the crop; if one product fails, the other products can help offset the economic loss,

Different techniques are used to extract particular chemicals. In general, polar solvents extract biologically active compounds and other

reactive chemicals, including dyes, antioxidants, and adhesives. Nonpolar solvents yield

compounds that are useful as lubricants,

waxes, and elastomers. The water or acidic

aqueous fraction may provide polysaccharides

such as gum or pectin and some water-soluble

protein. The residue from extraction is comprised of cellulose, hemicellulose, protein, and

lignin (if present). This material maybe burned

as fuel, used as livestock feed, fermented to produce industrial chemicals, or the fiber maybe

removed and used for pulp, paper, or fabric.

Native Plants, Inc. (NPI) has been studying

the showy milkweed (Asclepias speciosa) as

part of a program to investigate plants as new

sources of commercial chemicals. This species

was chosen for study because it is distributed

over a wide range of climates and soil types.

It is an herbaceous perennial found throughout

the Western United States, from the Mississippi River to the Pacific Ocean, and from central Alberta and Saskatchewan to central Oklahoma. Milkweed is a potential crop for areas

of low rainfall. For example, A. speciosa can

be grown easily in the western Great Plains,

where overuse of the ground water stored in

the Ogallala aquifer is requiring a shift from

irrigated to dryland agriculture. Milkweed

eventually may provide farmers with a substi-
26 . Plants: The Potentials for Etracting Protein, Medicines, and Other Usefu/ Chemicals—Workshop Proceedings

tute for irrigated crops or an alternative to

other dryland crops (e.g., dryland wheat, grain,

sunflowers, and sorghum) grown there. Most

of NPI’s work has been on milkweed’s photochemistry and extraction procedures. Although

some research has been done on agronomy and

crop storage, a great deal more is needed. In

addition, the economic viability and ecological and social impacts of developing milkweed

as a crop need to be examined carefully.

Fractionation of milkweed produces the following extracts with commercial potential:

pigments, rubber, and triterpenoids from nonpolar solvent extraction; inositol and sucrose

from polar extraction; and pectin from the

acidic aqueous extract. The residue left after

extraction consists of fibers that can be marketed for various commercial uses and fibrous

material that is suitable for livestock feed. The

material that can be used for feed represents

70 percent of the original plant biomass. It is

equivalent to alfalfa in protein content and

quality and in digestibility for sheep, but must

undergo exhaustive solvent extraction or heat

or acid treatment before it is rendered nontoxic.

Before commercialization of milkweed can

be successful, much additional research on

agronomy, harvesting, and crop storage is

needed. Small test plots have been established

by NPI in Utah, New Mexico, Texas, and Kansas. Attempts to establish stands elsewhere

were unsuccessful and problems with controlling weeds and obtaining uniform stands were

encountered. Developing effective methods of

weed control, especially when the milkweed

plants are still seedlings, is critical. Harvesting

research indicates that plants can be harvested

with standard farm equipment such as that

used for alfalfa. Test plots gave yields of about

4.3 tonne/ha, but denser planting might be expected to yield between 6.7 and 9.0 tonne/ha.

Storage tests indicated that although the nonpolar extractable remain stable, the polar extractable deteriorate over time when harvested material is stored. Covering the stored

material alleviates the problem considerably.

Storing the crop so that commercial processing could take place throughout the year would

provide considerable financial savings in plant

capacity.

Several environmental constraints must be

considered before this crop is grown widely as

a commercial crop. A major concern is that the

arid and semiarid areas where milkweed cultivation has been tested are highly susceptible

to erosion, especially by wind. The effectiveness of zero till, crop overseeding, sod culture,

narrow stripcropping, and various other options should be evaluated. Another problem to

be considered is loss of soil nutrients caused

by removal of plant material. Nitrogen will

have to be replaced by commercial fertilizer

and possibly organic manure from cattle feedlots. Some pest problems should also be anticipated. Aphids are serious pests of milkweed

and may become an economic liability in milkweed plantations. Pest control using natural

predators and both natural and synthetic insecticides should be investigated. The danger

of milkweed itself becoming a pest is an important consideration. Milkweed could cause

considerable problems by spreading to neighboring fields planted in other crops. Wild

populations of milkweed cause significant

problems as weeds in some agricultural fields

of Minnesota.

Major technical constraints will affect the

profitability and competitiveness of milkweed

compared with other crops. First, commercial

extraction and purification of inositol and pectin (sweeteners), which together represent 58

to 73 percent of the total estimated value of

milkweed products, are not yet commercially

viable. Proto-commercial processing has uncovered other processing problems that must

be resolved, and development of more efficient

methods for detoxifying the residue for livestock feed is needed.

NPI calculated milkweed production costs

using a 2-hectare research plot. The costs were

found to be greater for milkweed than for dryland wheat or grain sorghum. Weed control accounted for more than half of total production

costs. If weed control and harvesting techniques were improved, production costs could

be reduced significantly. The milkweed seeds
Ill.—Summary and Discussion of Each Workshop Paper . 27

used in the research were collected from wild

plants. Seed improvement through breeding,

selection, and denser spacing of the plants

could be expected to increase yields and improve the profitability of milkweed. The costs

of erosion-control practices, not considered in

the NPI analysis, should be factored in.

The total value of milkweed products ranges

from $511 to $645 per tonne. These figures

represent only the market value of the processed goods. Because no figures are available

on processing costs to extract these materials

from milkweed, market values indicate little

about crop profitability. Processing costs may

be considerable. For one thing, the costs of recovering extraction chemicals might be very

high. As already mentioned, extraction and

purification of inositol and pectin are difficult

and expensive; economically viable techniques

have not yet been developed. The other highvalue products are triterpenoids, sucrose,

fibers, and livestock feed. It is questionable

how effectively sucrose and fibers from milkweed could move into the high-volume, wellestablished markets for these products. Livestock feed may prove to be competitive with

other feed crops, especially on lands where

these crops are unproductive such as areas of

the western Great Plains. The potential of milkweed to substitute for fossil fuels as sources of

hydrocarbons and chemical feedstocks can not

be assessed from the information given. Before

the economic feasibility of milkweed production can be predicted with any accuracy, more

data on the costs of these products and the

costs of producing alternatives from milkweed

are needed. If milkweed products were to be

moved into fossil-fuel related markets or other

large-demand markets, large acreages of semiarid land might be converted to milkweed production. Ultimately, however, the competitiveness of milkweed as either a small-demand

“specialty” crop or a large-demand crop is contingent on the marketability of the products.

A great deal more marketing research must be

done to assess milkweed’s economic feasibility.

The scale of production is a vital consideration to the economic viability of milkweed.

Large-scale production probably is needed to

make it a profitable enterprise. Both the “specialty” or high-cost products (e.g., inositol, pectin) and the low-cost products (e.g., livestock

feed, fiber) require large-scale production.

Large amounts of milkweed are necessary to

produce even small amounts of the more valuable products, and enough of the large-volume

products must be available to capture a portion of their markets. If the economic viability

of milkweed were dependent on inositol and

pectin, care would have to be taken to avoid

flooding the markets. A balance that could satisfy the demands of the low- and high-volume

products would have to be reached. As will all

new crops, scaling-up from pilot studies to

commercial production would be the most difficult step and would be contingent on milkweed’s attractiveness to investors.

If milkweed were to become commercially

viable, it could provide many benefits. Although dryland wheat, grain, sorghum, and

sunflowers are grown on the western Great

Plains, the productivity of this area is not high

in its contribution to total U.S. crop production. Substituting milkweed for these crops,

therefore, would not reduce seriously the total

production of traditional U.S. food and fiber

crops. The western Great Plains is a cattlefeeding center. If milkweed were to replace

some of the crops grown there for livestock

feed, it could continue to supply feed necessary to support this industry. Milkweed could

provide farmers with an alternative crop, thus

freeing them from their dependence on commodity goods. Grain prices have remained stable, but operating costs have risen, so that the

region’s farming economy is severely depressed, If proven to be profitable, milkweed

would provide an alternative that could facilitate the region’s economic recovery. Another

potential benefit would be import substitution.

If the extraction problems were solved, milkweed could fulfill the U.S. demand for inositol,

all of which is imported. Milkweed triterpenoids could substitute for some imported oils

or waxes and for all domestically produced and

imported pectin.

Although development of milkweed as a crop

would have many benefits and at this stage has
-

28 ● p/ants : The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

some promise, many economic, technological, crop. Its potential will have to be examined in

agronomic, and ecologic problems must be re- relation to present crops as well as new aridsolved before it could be a commercially viable and semiarid-land crops being studied.

INSECT REPELLANTS, ATTRACTANTS, AND

TOXICANTS FROM ARID/SEMIARID LAND PLANTS

From the time of the early Remans until 1900

only three efficient plant-derived insecticides—pyrethrum, hellebore, and nicotine—

have had widespread use. Advances in chemistry and improved screening techniques,

however, have led to the discovery of many

plant-derived insect toxicants, repellents, attractants, feeding deterrents, growth inhibitors,

and sterilants since the turn of the century.

Some of these active compounds may be developed commercially and would expand the

range of available products for insect pest control. New plant-derived insecticides might provide substitutes for some synthetic insecticides

that are ecologically disruptive and for others

to which insects have developed a resistance.

Arid- and semiarid-land plants are good

sources of insect toxicants and related compounds. Some of these biologically active

chemicals are produced by the plants as defenses against pests and pathogens. In environments of climatic stress where plant growth is

slow, insect attack can be particularly debilitating to a plant. A strong defense system may

be critical to survival and probably has been

an important factor in the evolution of arid/

semiarid-land plants. Not only are these plants

good sources of insecticides and related chemicals but they are adapted to areas that are

marginal for production of traditional food and

fiber crops. Arid/semiarid-land plants with

commercial potential offer the opportunity to

expand agriculture on land that is unproductive for established crops. In addition, perennials such as the neem tree or mamey apple

may be ecologically preferable to other crops

on arid and semiarid lands which commonly

are highly susceptible to erosion.

The USDA Biologically Active Natural Products Laboratory in Beltsville, Md., has been

studying plants as potential commerical

sources of insect toxicants, deterrents, and attractants. Seven plants appear to be particularly promising. Most of these plants have been

used locally in different countries for various

purposes including insect control. The plants

represent potential multiproduct crops for the

United States and developing countries. Most

of the work done by USDA has been on extraction and application of the chemicals. A great

deal of applied research on agronomy, commercial processing, and marketing is needed

before commercial production of most of these

species would be possible.

Calamus

Calamus, Acorus calamus is a semiaquatic

perennial that can grow on dry land. The roots

have been used from ancient times in India and

Japan for the treatment of a variety of ailments

and as an insect repellant and toxicant. The different varieties—American, Indian, Japanese,

and European—have different insecticidal

characteristics. Commercially available oils

from the Indian and European varieties are obtained either by steam distillation or solvent extraction. They are repellent or toxic to clothes

moths, house flies, fleas, lice, mosquitoes, and

many stored-grain insects. The Japanese variety causes sterility in male house flies. Oil from

the Indian variety is highly attractive to Mediterranean fruit flies, melon flies, and oriental

fruit flies. The roots are used in China as an

insecticide and vermifuge. The component primarily responsible for sweetflag’s repellency

and sterility is B-asarone which can be synthesized more cheaply than it can be extracted

from plants. It is effective against the rice

weevil, probably the most damaging insect pest

of stored grains. Another active component,
Ill.—Summary and Discussion of Each Workshop Paper ● 29

asarylaldehyde, is commercially extracted from

the plant material. These two compounds probably would be useful as fumigants for protecting stored grain from insects because they

permeate grain-filled storage areas without

leaving residues on the grain after the areas are

ventilated. Other potential uses of Calamus

compounds are for tuberculosis treatment, as

a germicide, and in perfumery. One constraint

to using Calamus chemicals is that B-asarone

has a depressant effect on the central nervous

systems of mice, rats, and monkeys. Although

these pharmacological properties may limit use

of Calamus oil to certain applications, they

should not prevent use of the oil for agricultural insect control and possibly for medical

purposes.

Big Sagebrush

Big sagebrush, Artemisia tridentata, is a

multibranched perennial that is the dominant

plant of the Great American Desert. It has been

cultivated in the West since 1881 as a fodder

plant for range cattle. The brittle branches

sometimes are used for thatch by Indians, the

seeds are ground into a meal by the California

Indians, and a pollen extract is used against

hay fever. In the past, Artemisia has had various insecticidal uses. For example, sagebrush

leaves and shoots were placed in granaries to

protect stored cereals from weevils and other

pests, and the water in which they were

steeped was used to kill or repel insect larvae,

fleas, and locusts. An extract from sagebrush

is effective as a feeding deterrent against the

Colorado potato beetle, a pest of growing economic importance. This pest’s resistance to insecticides applied in potato-growing areas is

an increasingly serious problem in several

areas of the world, and this resistance probably

will become more common. Only one of the

compounds responsible for the feeding deterrent activity has been identified. It has not been

synthesized and it is unlikely that synthesis

would be economically feasible. However, the

crude, unpurified extract could be sprayed directly on crops, although the potential ecological effects of doing so must be assessed first.

Neem

Neem, Azadirachta indica, a common tree

of dry scrub forests in India and Burma, grows

on poor soils in hot, dry areas. Although all

parts of the tree are repellent to insects, extracts of the seeds are outstanding as repellents

and feeding deterrents for a broad spectrum

of economic agricultural and household insects

(e.g., Colorado potato beetles, Japanese beetles,

scale insects, cotton bollworms). Seed extracts

deter at least 25 species of crop pests in the

United States from feeding, inhibit the growth

and development of others, and render others

sterile. These compounds seem to be nontoxic to man, animals, and plants. Because they

are absorbed by the plant tissue, they offer

relatively long-lasting protection to crops

even after rain showers of high intensity. Three

antifeedants have been isolated from neem.

The most potent is effective against a variety

of insect pests native to the United States. This

chemical cannot be economically synthesized

because its structure is so complex, but it can

be extracted in pure form.

Neem is a source of many potential products

in addition to insect antifeedants and repellants. Almost every part of the neem tree is

used medicinally in India. Oil can be extracted

from the seeds for soap, wax, lubricants, and

lighting and heating fuel, and the residue can

be used as an organic fertilizer. Other parts of

the tree are used in various countries for commercial products, including timber and cabinetry wood, tannins, a toothpaste ingredient,

and livestock fodder. Neem production could

sustain cottage industries in Asia and Africa

and provide a base for large commercial operations in the United States and Central and

South America.

Neem plantations have been established in

northern Cameroon, Nigeria, Gambia, India,

Honduras, and some Caribbean islands. The

U.S. Peace Corps is encouraging neem cultivation in Cameroon and Gambia, and USDA has

started a program to develop neem commercially in Puerto Rico and the U.S. Virgin

Islands. Constraints to commercial develop-
30 Ž Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

—

ment include short-term seed viability, rapid

photodegradation by sunlight of the major active principle after field application, unpleasant

smell of the seed oil, frost susceptibility, poor

growth on poorly drained soils, and poor agroforestry potential because of interference with

other crops and vice versa. Despite these constraints, cultivating and processing neem seem

promising. USDA is carrying out the major

basic research on extraction and application

of the chemicals. Universities and government

agricultural institutes in India are focusing on

applied aspects (i.e., agronomy, product uses,

marketing) of commercially developing neem.

Heliopsis Longipes

Heliopsis longipes, a perennial herb in the

aster family, is native to Mexico. Heliopsis

roots have been used locally in Mexico as a

spice, medicine, anesthetic, painkiller, and an

insecticide against warble larvae found in cattle wounds. Root extracts have also been effective against houseflies, mosquitoes, body lice,

bean weavils, and other household and agricultural pests. The active ingredient has been

isolated, identified, and prepared synthetically, but extraction is more economical than is

synthesis. Some transplanting and cultivating

experiments using wild plants have improved

plant biomass yields. However, in spite of the

succulent character of the roots, they dry out

when exposed to air and will not grow when

transplanted. Therefore, care must be taken

when transplanting wild plants that the roots

are kept moist or plants are replaced immediately.

Mamey

Mammea americana is an edible fruitbearing tree found in Latin America and the

Caribbean. The flowers, fruits, seeds, and

leaves are effective against a wide variety of

insect pests including melonworms, fleas,

ticks, lice, fall armyworms, mosquitoes, and

cockroaches. Two major insecticidal compounds have been isolated and identified, and

methods to extract them have been developed.

People have used the plant for many other uses,

but no serious attempt has been made at export or commercial production. The wood is

used in construction and cabinetmaking; the

flowers are used to make a liqueur in the

French Antilles; the fruit is eaten raw or is

stewed and made into a drink or candles; and

gum from the bark extracts chiggers from the

feet, The tree is cultivated on Caribbean

islands, and in Mexico and Central and South

America for the edible fruit. Mammea’s potential as a commercial crop in southern Florida,

Puerto Rico, and the U.S. Virgin Islands should

be investigated.

Basil

In addition to its widespread use as a spice,

Ocimum basilicum, or sweet basil, is recommended for use against gastric disorders, malarial fevers and skin diseases, and for insect

control. The oil from basil is an effective repellant and larvicide for mites, aphids, and

most species of mosquitoes; a growth inhibitor

for milkweed bugs; and an attractant for fruit

flies. Most repellant compounds in the oil have

been identified. The oil content of plants varies

depending on soil fertility and weather immediately preceding harvesting. Because extraction is simple and inexpensive, synthesis is not

commercially practical. The plant is cultivated

easily and can be grown and its oil produced

in many places in the United States.

Mexican Marigold

Tagetes minuta is an annual that is native to

Central and South America but also grows in

parts of East Africa, India, Eastern United

States, South Africa, and Spain. The oil produced by the seed, leaves, and flowers is

strongly repellent to blowflies and is useful in

the Tropics as a blowfly dressing for livestock.

The leaves are used locally in Africa and India to repel mosquitoes and safari ants. The oil

is more toxic to mosquito larvae than DDT. The

plant also has potential medical uses and the

roots exhibit fungicidal and nematocidal activity. An extraction method for the essential oil

has been developed. Although two larvicidal

compounds and the growth deterrent can be
III.—Summary and Discussion of Each Workshop Paper ● 31

synthesized, laboratory synthesis of several of

the pesticidal compounds gives low yields and

unreliable results. Because large-scale cultivation of the plant should be feasible, extraction

of the essential oil seems to have the greatest

commercial potential.

Marine plants are represented both by seaweeds, macroscopic forms that mainly live in

shallow coastal waters, and by phytoplankton,

free-floating, widely distributed unicellular

plants. Although a few flowering plants (angiosperms) are abundant in shallow waters, the

majority of marine plants are algae, typified by

their lack of a vascular system. Taxonomically, algae are highly diverse. Their highly

specific coloration has served as a basis of

classification; marine algae are divided into at

least 12 distinct groups based on color (e.g., red

seaweeds, brown seaweeds, blue-green algae,

etc.). While no precise estimate has been made,

it is thought that well over 100,000 species of

marine algae exist. Biogeographically, marine

algae live in all parts of the ocean and frequently are found in extremely high concentrations.

Although precise figures are difficult to substantiate, the primary productivity of 1 acre of

the marine environment may be twice that of

a Midwest cornfield.

Marine plants have evolved unique and highly specialized biochemical pathways to adapt

to their unique seawater medium and survival

pressures. The marine environment is rich in

chloride and bromide salts and other chemical

entities such as sulfate. Marine plants use these

elements in biosynthetic processes to produce

compounds that are unique to the marine environment. Many marine plants have evolved

toxins and deterrents as protection against

abundant and freely migrating predators. Even

though the same evolutionary pressures have

produced similar responses in terrestrial

plants, the defensive chemicals from marine

plants are novel and represent interesting new

chemical species that are unprecedented in terrestrial sources. Other chemicals represent

adaptations to the physical environment such

as wave shock and motion. For example, complex polysaccharides (complex sugars) act to

reduce the surface tension of seawater. These

constituents, too, are highly specific to marine

algae.

Marine algae have been used in different

countries for a long time as sources of foods,

food thickeners and flavorings, animal fodder,

soil manure, potash, and herbal medicines. For

example, “Nori” and “Wakami” have become

integral parts of Japanese diets, and over 18,000

tonnes of Nori are commercially produced

each year. Numerous species of marine algae

are used in China as herbal medicines to treat

many maladies ranging from intestinal problems to sunstroke.

A classical use for seaweeds has been the extraction of halogens and potash. Brown algae

were used for several decades as the major

source of iodine, and the red seaweeds were

used occasionally for deriving bromine. The

U.S. Pacific coast between 1910 and 1930 was

the site of a flourishing potash industry based

on the high potassium concentrations found in

local brown algae. The uses of marine algae as

sources for elemental halogens, potash, and

crude food-thickeners largely were curtailed

by the mid-1900’s as other, more cost-efficient

sources were developed. But also during this

period, many currently used algal products,

particularly algal polysaccharides, became established.

A well-established industry in the United

States now harvests marine seaweeds and extracts agar, carrageenan, and alginate. Agar is

found in many species of red algae and is used

mainly as a gelling agent and thickener in

foods but also as a biochemical adsorbent, culture and nutrient medium for bacteriological

research, and major nutrient medium for the

industrial production of antibiotics. Carrageenan, which is also extracted from red algae, has

widespread use within the food industry. The
32 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

total annual market value of polysaccharides

derived from red algae is about $200 million.

Alginate, extracted from brown seaweeds, is

particularly valuable for incorporation into industrial products and processes. It is used for

its thickening, emulsion stabilization, and gelling properties.

Even though the majority of marine algal

products come from the readily collected

macroscopic forms, several products are being

produced by the culture of unicellular forms.

The green alga Dunaliella, for example, recently has been established in mass culture as a

commercial source for glycerol (glycerine) and

the orange pigment beta-carotene. Glycerol is

used in the manufacture of many products

(e.g., printing ink, antifreeze) and beta-carotene

is used to impart color and provide vitamin A

in animal feeds and human foods such as margarine and is also used as a sunscreen agent.

Several algal species have been used consistently in the biomedical sciences. In particular,

active components of red algae Digenia

simplex and various Chondria species are extracted, purified, and marketed as drugs in

Asia. No other examples of successfully algaederived pharmaceuticals exist, but there certainly is a great potential for further development in this area.

Even though relatively little basic chemical

research has been performed on marine algae,

mass culture techniques, both in the ocean itself and in controlled coastal facilities, have

great potential to provide industrially significant quantities of marine algae. Funding from

the Department of Energy (DOE) through the

Solar Energy Research Institute (SERI) and

several other agencies has supported work on

requirements for effective algal growth. Marine

algae probably will be a focus of considerable

attention over the next decade as we investigate new resources for both energy and industrial product development.

Although relatively few algal products have

been developed successfully by industry, the

potential for the discovery and development of

a plethora of unique new products seems unlimited. A few of the most notable areas for exploitation in the near future are summarized

below.

Biomass Conversion

Work already has begun on assessing algae

as sources of biomass for conversion to methane gas, ethanol, and other useful chemicals.

Algae are efficient photosynthetically and are

cultured conveniently in the open ocean,

ponds, or controlled culture vessels. However,

problems with fertilization of cultured seaweeds must be solved. Biomass conversion

processes are not cost efficient, but continuing research is needed so that the technology

will be available when required in the future.

Pharmaceutical Development

Although numerous biomedical uses for algal

polysaccharides have been established, the

majority of applications involve use of their

physical properties rather than their physiological activities. A surprising percentage of algal

polysaccharides, however, show antiviral activity. For example, a red seaweed extract contains an antiviral compound that is effective

against Herpes simplex, a virus responsible for

a disease that has reached epidemic proportions in the United States. Several substances

with antibiotic and antitumor activity have

been isolated from macroscopic seaweeds. Although few comprehensive studies of microscopic algae have been reported, some of these

algae exhibit antimicrobial activities and are

known to produce powerful toxins. However,

almost no information exists on the pharmacological potentials of the tens of thousands of

microscopic marine algae mainly because of

the difficulty in purifying a single species of

unicellular algae and growing it for biomedical

studies. Much could be learned from such research.

The slow rate of developing new marine

pharmaceuticals clearly can be linked to the

limited involvement of the major pharmaceutical companies. Pharmaceutical firms do not

have in-house expertise and marine biological
Ill.—Summary and Discussion of Each Workshop Paper ● 33

laboratories in the past have not employed

scientists with biomedical expertise. This is

changing, however. Major programs have developed under the Department of Commerce’s

Sea Grant Program. The Sea Grant effort in biomedical development is an effective blend of

academic and industrial (basic and applied) research that is yielding fruitful results. The Sea

Grant project, “Marine Chemistry and Pharmacology Program, ” at the University of

California, for example, has discovered more

than 75 pure compounds with potential biomedical use and the project has emphasized

collaboration with the pharmaceutical industry. This collaboration is the vital link to ensure that basic marine research finds its way

to the industry that is capable and interested

in developing new products.

Other governmental agencies have had more

limited involvement in marine biomedical development. For example, the National Cancer

Institute has dedicated significant resources

toward the isolation of new antitumor drugs.

Here again, the need to involve basic marine

scientists to locate, identify, and quantitate

suitable marine species for study was underemphasized, and considerable difficulties were

encountered.

Agricultural Chemicals

Many synthetic pesticides are halogenated

compounds. Since halogenation is a natural

process in marine plants, the compounds produced are likely to possess agrichemical activity. Initial collaborative investigations indicate

considerable promise. Of 12 algal compounds

assessed in herbicidal and insecticidal bioassays, 9 showed some activity, and 1 was nearly equivalent to DDT in insecticide activity.

Here again, the success in developing marine

algal agrichemicals lies in developing a close

relationship between academic and industrial

research. A limitation on commercial development of marine extracts is that little Government funding is available outside of USDA.

Agricultural research funding should be expanded in the United States to include a greater

component of academic research.

Food and Food Products

In addition to agar, carrageenan, and alginate, marine algae are recognized sources of

numerous useful food products, including

cooking oils. Although the seaweeds usually

are low in protein, many phytoplankton are

rich protein resources. The blue-green algae

are potential protein resources, and one bluegreen algae, Spirulina, has already been marketed as a health food.

Enzymes

Marine enzymes, while almost completely

unknown, could be used beneficially in industrial processes.

Industrial Chemical Feedstocks

Both macroscopic and microscopic marine

algae could be cultured to yield hydrocarbon

mixtures that could be used as diesel fuel

without further purification. Other compounds

found in most marine algae could be used in

the plastics industry. Notwithstanding the

work on agar, carrageenan, and alginate, phytoplankton, in general, have been virtually

unexplored for their polysaccharide components even though it is highly conceivable

that they could yield new and important

products.

Needs for Developing

Marine Algal Resources

Small-volume products, such as a specialty

pharmaceutical, could be developed from naturally occurring populations but, in general,

effective use of marine algal resources, especially unicellular algae which cannot be collected in pure form, must be coupled with mass

culture technology. Mass algal culture and

product derivation should be developed keeping in mind multiple-product development. The

algal resources that should be considered for

development are those that produce more than

one marketable product to offset the relatively high production costs.
34 Ž Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

A basic problem in considering development

of marine algal resources is that there has been

insufficient research on potential products

from algae. Although a significant number of

chemical investigations have been conducted

on seaweeds, there have been few on unicellular algae. Considerable resources are being

devoted to developing algal-culture technologies, but generally these studies are not predicated on a solid knowledge of algal chemistry,

genetics, nutrition, and reproduction. In addition, mass culture techniques must be refined.

Biotechnological advances, particularly in

the field of marine genetics, can be expected

to have sizable impacts on use of marine resources. Marine products and biochemical

processes are unique, and this unique gene

pool could be highly useful in future product

development.

A significant problem lies in the poorly developed working relationships between Government, universities, and appropriate industries. Government funding agencies have

difficulty supporting applied research, particularly as it may benefit a single private enterprise. The university system finds its relations

with industry strained by patent and proprietary information problems. Close cooperation

between these entities will be necessary, such

as has been developed by the Sea Grant Program. As this tripartite collaboration develops,

it seems likely that marine algal species will

become major sources of future products.

ANTICANCER DRUGS FROM THE MADAGASCAR PERIWINKLE

Although literature sources cite 3,000 plant

species used or recommended for cancer treatment in different parts of the world, only one

species has been used to produce a commercial cancer-chemotherapy drug. This plant is

the Madagascar periwinkle, Catharanthus

roseus. It is an herb or subshrub found

throughout the Tropics and cultivated as a garden plant worldwide. The development of the

periwinkle anticancer drugs from isolation and

purification of several Catharanthus alkaloids

to laboratory and clinical testing and subsequent marketing of two of them represents

a tremendous success story in the field of plantderived pharmaceuticals. In the short time

since first clinical use, these alkaloids have

become two of the most valuable cancer chemotherapy treatments available.

The Madagascar periwinkle was one of 440

plants selected for study in an Eli Lilly plantscreening program for plant-derived drugs.

The plants were chosen on the basis of carefully assessed reports of folklore use and reported

alkaloid contents. Alkaloids, complex nitrogencontaining plant compounds, are often physiologically active. They are the most common

active ingredients in many plant-derived medicinals. C. roseus was reported to contain

alkaloids and folklore uses indicated that it contained biologically active compounds. Past use

of the plant had been based on its blood-sugarlowering properties, suggesting to Eli Lilly

researchers that it might provide a substitute

for oral insulin. When tested at Eli Lilly, however, the plant initially did not exhibit hypoglycemic activity but did show strong and repeated antitumor activity when subjected to an

antileukemia model. Ironically, the periwinkle

had not been one of the 3,000 plants cited as

cancer treatments in reports of folklore use.

Standard isolation and purification techniques were not successful in extracting the

antitumor agents from the plant, so new extraction methods were devised. Using these new

techniques (selective extraction followed by

column chromatography and gradient pH technique), Eli Lilly isolated 55 alkaloids from C.

roseus. A total of 74 alkaloids, 3 of which were

previously unknown, have been isolated from

mature periwinkle plants, and 21 additional

compounds have been isolated from immature

plants. This extraction work and subsequent

sterochemical research to determine the

alkaloids’ chemical structures represent significant advances in the field of photochemistry.
Ill.—Summary and Discussion of Each Workshop Paper ● 35

Two of the periwinkle alkaloids that showed

potential as antitumor drugs have reached the

marketplace. These are leurocristine (LC)-

whose generic name is vincristine and is

marketed by Eli Lilly as ONCOVIN-and vincaleukoblastine (VLB)-known generically as

vinblastine. Although LC and VLB are closely

related chemically, they have different potencies against tumors because of minor differences in their molecular structure. Leurocristine, called a “miracle drug” because it was

placed on the market only 4 years after initial

discovery and is extremely valuable in cancer

chemotherapy, was responsible for a resurgence of interest in plants as sources of antitumor compounds. LC is most effective in treating childhood leukemia of the lymph system;

alone it can induce a 50-percent response rate

in children with acute lymphocytic leukemia,

and in combination therapy gives a 90-percent

response rate. It is also effective against a variety of human cancer, including Hodgkin’s disease, breast cancer, and primary brain tumors.

VLB is used mainly in treating lymph tumors,

especially in Hodgkin’s disease patients. It

shows a 70- to 80-percent response rate in patients with lymphoma, is highly effective

against testicular tumors, and shows activity

against various other cancers.

These two compounds and other dimeric

Catharanthus alkaloids showing similar antitumor activity represent a new class of antitumor agents. Although their mechanism of action still is not completely understood, it seems

to be based on disrupting cell division, thus arresting tumor growth.

Chemotherapy treatments have improved

over the last two decades so that they are effective alternatives for or additions to radiation

and surgery as cancer therapies. Much of the

improvement in chemotherapy is the result of

combination drug treatments in which various

drugs with different mechanisms of action are

used together. The periwinkle alkaloids are important in these multidrug therapies and have

been key elements in the increasing sophistication of cancer treatments.

The potential of Catharanthus roseus alkaloids as medicines is by no means exhausted.

A great deal of chemical work has yet to be

done both on LC and VLB and on the other periwinkle alkaloids showing antitumor activity.

One alkaloid that seems particularly promising

and needs more research is leurosidine. Clinical tests for an experimental leukemia model

in mice indicate that leurosidine is the most

experimentally active Catharanthus antitumor

alkaloid. However, the yields from periwinkle

plants are low and high doses are needed for

testing, so sufficient amounts of leurosidine for

comprehensive clinical trials have never been

stockpiled. Another compound that has not

been fully investigated is an unidentified

chemical called “super leurocristine” which

displays 300 times more antitumor activity than

leurocristine/leurosidine fractions. This was

never clinically tested and the high cost to

stockpile the active fraction for testing now is

considered prohibitive.

Chemical derivatives of Catharanthus alkaloids also deserve additional research. Since

slight chemical alteration may produce dramatic changes in dose-limiting toxicity of a

compound, work on chemical derivatives may

uncover potentially marketable compounds

with more benign side effects than the original compound.

Another area that should be explored further

is the conversion of leurocristine to vincaleucoblastine. The yield of leurocristine from

periwinkle plants is 0.0003 percent, the lowest

yield of any commercially used medicinal

alkaloid. The yields of VLB are considerably

higher, and since the chemical structures of the

two are closely related, it maybe possible and

economically beneficial to convert VLB into

leurocristine. This conversion has been done

successfully in the laboratory, but a great deal

more work must be done before it can become

a commercially viable operation.

Attempts to synthesize VLB and LC have

been unsuccessful. This should continue to be

a research priority. Until synthetic equivalents
36 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

can be produced, the active compounds will

have to be extracted from periwinkle plants.

Catharanthus roseus plants were initially collected from the wild. As it became apparent

that there would be a demand for thousands

of tons of plant material, periwinkle cultivation

began on farms in India and Madagascar. To

avoid the risk that the supply of raw material

might be cut off and to guarantee an uninterrupted supply of plants, cultivation was started

in Texas.

The success of the work on the Madagascar

periwinkle was dependent on two major factors: careful plant selection and the availability of an appropriate test system (an experimental mouse tumor) to monitor the effectiveness

of purified active compounds. Plant selection

was based on alkaloid content reported from

folkloric use. Folkloric use can be a valuable

indicator of the desired chemical activity if

care is taken in interpreting the reports. If not,

such reports can be misleading. Another method by which to choose plants for screening is

random selection. The success of random selection could be improved by considering botanical and chemotaxonomic relationships between the plant to be tested and plants of

known photochemistry and biological activity. An experiment mouse tumor served as an

appropriate biological test system to monitor

the purified alkaloids for the desired activity.

Perhaps the major lessons to be learned from

the research and development (R&D) of Catharanthus alkaloids as anticancer drugs are that

pharmaceutical drugs can be obtained from renewable resources rather than petroleumderived synthetics and the developing new

plant-derived drugs can be profitable. Despite

the potential of plants for providing valuable

new drugs and high profits to the companies

developing them, U.S. pharmaceutical firms

have eliminated their plant-screening programs

and the Federal Government has discontinued

its program for plant-derived anticancer

drugs. * This disinterest is not because the

potential for finding valuable drugs in plants

has been exhausted. Only a tiny proportion of

the Earth’s higher plant species has been phytochemically screened, and these species represent a bank of potentially important drugs. As

already mentioned, more than 3,000 plants

have been cited as possible anticancer treatments, not to mention known activity of numerous other plants that could be valuable for

other medical uses. This disinterest in plant

screening for pharmaceuticals is not universal.

The Germans, Japanese, Russians, and Chinese

have major investments in exploring potential

plant sources for pharmaceuticals and other

chemicals. Perhaps the reasons for the neglect

of this research in the United States should be

examined and decisions to discontinue work

reconsidered.

*See the paper by Farnsworth and Loub in the appendix,

STRATEGIC AND ESSENTIAL INDUSTRIAL MATERIALS FROM PLANTS

The United States depends on other nations

for many materials and manufactured products

important to U.S. industry, including agriculturally produced plant substances and mined

materials. Some of these products are or could

be agriculturally produced in the United States

and used as industrial materials or as renewable replacements for petroleum as sources of

feedstock in the chemicals industry.

Some industrial materials are classified as

“strategic, ” or critical to national defense.

Three “strategic” industrial materials are

castor oil and sperm whale oil, * which are

high-quality lubricants, and natural rubber.

Law requires that sufficient supplies of these

materials be acquired and stored in the United

States to meet national defense needs in case

of war. “Essential” materials are those required

*The Endangered Species Act of 1970 prohibits production

or importation of sperm whale oil so it is not stockpiled in the

United States. A substitute for this high-quality lubricant must

be provided. Jojoba is a promising substitute.
III.—Summary and Discussion of Each Workshop Paper Ž 37

by industry to manufacture products depended

on daily. Essential materials include items

manufactured or extracted from plants (e.g.,

waxes, oils) and replacements for petroleum

used as feedstock in manufacturing synthetic

materials (e.g., plastics,. chemicals).

The United States imported an estimated $23

billion worth of agriculturally produced industrial materials and petroleum for feedstock

during 1979. Average annual growth in imports

for 1975-79 was 10 percent. The manufacture

of synthetic organic chemicals consumed about

470 million barrels of petroleum as feedstock

in 1978, valued at $15.1 billion. U.S. industry

purchased nearly $2 billion worth of agricultural imports, $3.5 billion worth of newsprint

and other paper products, and $2 billion worth

of chemicals extracted from plants and petroleum.

Technologically, it seems possible to produce

domestically nearly all the aforementioned imported agricultural products and materials and

to substitute domestically produced agricultural products for the 470 million barrels of imported petroleum feedstock, with a net savings

of about 270 million barrels of imported oil per

year. Table 1 lists some of the potential domestic crops and what they might replace. Sufficient research indicates that their domestic

production and use in the chemicals industry

Table 1 .—Potential Domestic Crops and Uses

Guayule

Cram be

Jojoba

Lesquerella

Veronia-Stokesia

Kenaf

Assorted oilseeds

Hevea natural rubber,

resins

High erucic rape oil and

petroleum feedstocks

Sperm whale oil and

imported waxes

Castor oil

Epoxy oils

Imported newsprint and

paper

Petrochemicals for

coatings and other

industrial products

SOURCE: Office of Technology Assessment.

are chemically feasible, agronomically possible, and economically viable, although more

agronomic and economic research must be

undertaken before definitive conclusions can

be drawn about their substitution feasibility.

Production of only one-third the annual domestic demand for strategic materials would eliminate the need to stockpile them, could save at

least $1 billion of public money over the next

18 years (otherwise spent in acquiring and

maintaining strategic stockpiles of natural rubber and castor oil), and could provide replacements for sperm whale oil. Producing 100 percent of the strategic and essential industrial

materials or their replacements might reduce

U.S. foreign outlays by about $16.5 billion annually at constant 1979 dollars and demand

levels.

Production of substitutes for one-third to onehalf the industrial materials purchased abroad

would demand about 60 million acres of cropland. The United States has about 413 million

acres of cropland and about 36 million acres

of pasture and other land in farms that easily

and inexpensively could be converted to crop

production. Another 96 million acres of land

could be converted to crop production with

more difficulty and expense. The Nation’s total

cropland base (land capable of sustained crop

production under intensive cultivation by

known methods) is therefore about 540 million

acres. According to USDA, about 462 million

acres of cropland will be needed in 2030 to

meet domestic and foreign trade demands for

food and fiber. This would leave 78 million

acres of the cropland base to meet other production needs. If 60 million acres were used

for industrial and strategic materials production, 96.8 percent of the Nation’s cropland

would be used.

The question of land availability must be examined carefully. The land resource base that

will be needed or available for food, fiber, and

industrial chemical crops over the long term

will depend on certain unpredictable circumstances including international trade (e.g., level

of export sales, price of petroleum); changes

in land productivity; and quantity and quality

of agricultural land being lost to urban devel-
38 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

opment, water impoundments, etc. Another

issue is the feasibility of converting farmland

and land in other uses to the production of industrial crops. Lands currently in agricultural

production could be converted to industrial

crops more easily than uncultivated lands and

lands owned or operated by nonfarmers. It

would be largely a question of the economic

tradeoffs of one crop against another. If a new

crop is sufficiently more profitable than an old

one, it probably would be planted. However,

the scant amount of information on motivations of persons owning farmland that is not

farmed indicates that much of this land is

owned for esthetic, recreational, or speculative

purposes and could not be shifted into agricultural production easily. In this case, putting

these lands into industrial crops is not a

straightforward economic issue. The land

would have to be leased or sold to farmers, and

this transferal of landownership or control

could be a constraint to new-crop development.

Another land-related question that should be

raised is whether a 100-percent” utilization rate

of the agricultural land base is optimal. Serious

thought should be given to possible land quality

degradation, especially from cultivating marginal lands. Clearly, some agricultural lands

could benefit from substituting a more ecologically suited crop for a traditional crop (e.g.,

crambe in areas marginal for corn or wheat),

but care must be taken that increased use of

the Nation’s agricultural land base does not

outpace development of appropriate cropping

systems that minimize ecological degradation.

In addition, the need for a land reserve that

could be tapped in the event of unforeseen

circumstances should be considered.

Current research on new crops is extremely

limited. Only guayule, jojoba, and crambe are

being grown on semicommercial scale acreages. Federal funding for research is greatest

for guayule because of its importance to the

military. However, the total 1981 public expenditures for guayule research totaled only $3

million. Research commitments to all other potential substitute commodities discussed here

were considerably less.

Little additional basic chemical research is

needed for these commodities. Chemical engineering to develop efficient, economical extraction and processing systems, however, is

needed. Because of the present lack of risk capital in the private sector, public support of such

research probably would be necessary if these

plant materials are to be commercialized. However, in 1982, the Office of Management and

Budget imposed rigid guidelines governing

Federal research and directed USDA to terminate any ongoing research of a commercial

nature. Byproduct-use research also will be

needed to assess commercialization potential.

The value of byproducts is unknown because

information on their potential uses is limited.

The greatest need for research on these potential commodities in the immediate future is

in the areas of plant breeding and agronomy.

Most of these new crop materials being grown

in research projects are from wild or nearly

wild plants. Genetic improvements are needed

to increase seed and oil yields and predictability of the plant under cultivation. Little

agronomic research has been done for potential new commodities other than crambe and

guayule.

The economic benefits of using domestic production to replace agricultural imports and to

substitute renewable agricultural materials for

petroleum as feedstock in the chemicals industry depend on:

● the relative costs of substitutes and current

sources of these materials,

● the degree of profitability in producing

new agricultural raw material, and

● the level of subsidization required by the

agricultural industry to meet national strategic and essential materials needs.

One study of the commercial feasibility of establishing a domestic rubber industry based on

guayule estimated that the price for imported

rubber and the costs of domestic production

will converge in the late 1980’s, making it

equally as attractive to produce the material

domestically as to import it.
III.—Summary and Discussion of Each Workshop Paper • 39

The primary consideration in substituting

agricultural commodities for petroleum as

feedstock in the chemicals industry is the price

of petroleum. In industrial uses, seed oils could

sell at a higher price per pound than petroleum

without increasing the price of the final chemicals produced because these plants yield relatively pure chemicals that could be used with

little processing. Extraction of the same chemicals from petroleum is complex and expensive. The economic viability of substituting

agricultural commodities for petroleum cannot

be assessed until semicommercial production

and prototype-scale extraction are undertaken

so that the values of the chemicals produced

can be compared. Genetic improvement could

make these substitutes more economically

competitive.

During recent years, the Federal Government

has spent between $7 billion and $14 billion

annually to subsidize production of commodities that are already in surplus. If this subsidy

were spent instead to encourage the domestic

production of imported plant materials or to

provide substitutes for petroleum feedstocks in

the chemicals industry, the average subsidy on

the 60 million acres required to reduce imports

by half would fall between $116 and $233 per

acre per year. If 60 million acres are used to

produce such commodities, on-farm employment could increase by about 155,000 jobs.

This also would generate indirect income and

employment benefits to agriculturally related

enterprises.

Evidence suggests that oil-conservation efforts in the United States and other importing

countries already have had major dampening

effects on world production and pricing. In the

event the world oil price decreased as the

United States switched to agricultural alternatives, the United States would have increased leverage with oil suppliers as long as

its option to substitute agricultural commodities were kept open.

Domestic production of imported agricultural materials and petroleum substitutes would

have foreign policy implications. Exporting nations would react unfavorably to U.S. import

substitution, whereas other nations importing

these materials would benefit from resulting

lower prices. It would be important for U.S.

domestic agricultural policy and U.S. foreign

policy on import substitution to be consistent,

and Federal policy makers would have to be

cautious about geopolitical problems that might

arise from Government support of import substitution efforts.

The key short-run issue for farmers, agricultural firms, and the Federal Government would

be whether to subsidize production of new

agricultural commodities instead of continuing to subsidize surplus production or support

agreements to take land in surplus commodities out of production. Incentives for consumers of intermediate industrial materials and

end-products to support substitution of domestically grown commodities would be lower

cost, assurance of continued supply, and

decreased price fluctuations.

Four domestic policy shifts would be needed

to move toward domestic control and production of strategic and essential industrial

materials:

1.

2.

3.

4.

from dependence on foreign nations for

agriculturally based strategic materials to

domestic supply of them;

to a national policy of encouraging agricultural research that has foreseeable commercial application, including participation with the private sector in commercialization activities, partly research and partly commercial in nature;

to spend Federal funds to support production of useful agricultural commodities

rather than supporting production of surplus commodities or pay for farmers to discontinue production; and

to look at domestic production of agriculturally produced materials as a way of

using our farm-production potential rather

than depending on foreign trade.

Sufficient resources should be committed to

the kinds of activities suggested hereto use or

discard, with just cause, the many development

options that exist for domestic production of

imported strategic and essential industrial

materials.
40 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

INFORMATION USEFUL TO PLANT-DERIVED DRUG PR0GRAMS

Higher plants are essential ingredients of a

large proportion of U.S. prescription and overthe-counter drugs. From 1959 to 1973, new and

refilled prescriptions containing plant products

represented 25 percent of all prescriptions dispensed from community pharmacies in the

United States. The dollar cost to the consumer

for prescriptions containing active ingredients

from higher plants was $1.6 billion in 1973. Adding an almost equal amount to this figure for

plant-derived drugs dispensed from other outlets (e.g., out-patient hospital pharmacies, extended care facilities, Government hospitals),

an estimated total cost to the consumer was $3

billion in 1973. The current annual cost to the

consumer for plant-derived drugs is estimated

to be at least $8 billion. In addition to the prescription drugs, the sale of herbal teas in the

United States is estimated at about $200 million

annually, and the sale of over-the-counter

(OTC) drugs obtained from plants is probably

at least $1 billion.

National Prescription Audit (NPA) data show

that 41 species of higher plants yield all of the

plant-derived prescription drugs. An additional

62 species of plants entered the prescription

market in the form of crude extracts with active principles. Less than 50 pure compounds

from plants were represented in the prescriptions analyzed. Virtually all of these compounds are produced commercially by extraction of plant material or by chemical modification of extracted plant compounds. Although

most of these drugs have been synthesized, synthesis is not commercially feasible, with few

exceptions.

Although much has been written in scientific

journals of this country and abroad that should

spark industrial interest to invest in research

on plant extracts, interest in this country has

declined. In 1974, the American pharmaceutical industry’s total research and development

budget for pharmaceuticals for human use was

$722.7 million, Only one firm was involved in

direct research to explore plants for new

drugs with an annual program budget less than

$150,000. Today, there are no U.S. pharmaceutical manufacturers involved in a research program designed to discover new drugs from

higher plants.

Of the developed countries, only West Germany and Japan pursue development of new

plant-derived drugs. West German studies are

supported by many small firms but have not

captured the interest of large pharmaceutical

companies. Japanese academicians receive

government and industrial support for research

on plant drugs, and Japanese pharmaceutical

firms have major research departments dedicated to the same goal. Scientific papers from

Japanese research laboratories relating to drugplant development outnumber those from the

United States by at least tenfold, and Japanese

patents for plant-derived biologically active

substances outnumber those from the United

States by a factor of at least 50.

Plant sciences have not had a voice in U.S.

corporate or high-level governmental decisionmaking, except in the area of basic agriculture.

Important decisionmakers connected with

drug development apparently are unaware of

the extent to which plants contribute to our

source of drugs. During the past three or four

decades, research administrators rarely have

been trained in plant sciences. Further, science

has advanced to a point where interest has not

been on the intact organism—plant, animal, or

microbe—but rather on the cell, cell contents,

and cell biochemistry. Typical industrial drug

development increasingly has involved synthesis of molecules based on structure-activity relationships, and natural product drug development has been restricted to antibiotic production by micro-organisms.

Most useful drugs derived from higher plants

have been “discovered” through scientific inquiry into alleged folkloric claims of therapeutic effects, although in recent years the random

collection of plants followed by pharmacologic

evaluation has been pursued. A major program

of the National Cancer Institute (NCI) involving the “screening” of plants randomly collected worldwide ended in late 1981. This pro-
III.—Summary and Discussion of Each Workshop Paper ● 41

gram, which was started in about 1956, tested

some 35,000 species of plants for antitumor activity in laboratory animals. Although a large

number of highly active agents were discovered by the NCI program, some remain to be

studied in humans and as yet none have been

approved for use in humans by FDA.

Industry’s development of useful drugs from

higher plants during the past 30 years has not

been more productive than Government efforts. Since 1950, pharmaceutical companies

have produced only three plant-derived drugs

that have reached the U.S. prescription market:

reserpine, vincaleukoblastine, and leurocristine. * The total number of industry research

dollars required to discover these drugs has

been miniscule compared with the cost of placing synthetic drugs on the market. One reason for

this might be that much of the unexplored flora

in the world is found in tropical or semitropical

developing countries that may be regarded as

unstable supply sources for an international

market. However, another country might serve

as a source of wild plants or plant supplies may

be obtained through cultivation or other techniques (e.g., tissue culturing). A second reason

industry cites for lack of screening and plantdrug development is that patent protection is

less secure with natural products than with

synthetics. There is little evidence to back up

this claim.

Data of value in organizing and implementing an effective plant-derived drug development program are difficult to obtain through

available online drug data bases or from published reports. In addition, much of the useful

pharmacological data on plant extracts were

published prior to the earliest data covered by

all available online data bases. Pharmaceutical

companies are reluctant to share data derived

from testing plant extracts, even if the data are

negative and are of no commercial interest to

the firms. Negative data are as important as

positive data in a broad plant-based development program; knowledge of past negative research can help other researchers in selecting

new plants for study without duplicating past

*See paper by Svoboda in the appendix.

work. NCI published negative data regularly

at the beginning of the plant screening program, but this soon ended.

If plants to be screened for a plant-derived

drug program are not to be screened randomly, they should be chosen on the basis of best

available information (table z). Information

sources will vary, but probably would include:

1. Ethnomedical data—anthropological writings, folkloric writings, popular books,

pharmacopoeias, etc.;

2. Experimental data on plants—abstracting

services (e.g., Chemical Abstracts), bibliographic online data bases, review articles.

After collection of available pertinent data,

drug development programs proceed through:

● plant collection,

● bioassay for evaluation of crude plant extracts,

● isolation and identification of biologically active chemicals from plants, and

● clinical evaluation and marketing.

Few pharmacologists are experienced in evaluating crude plant extracts or are interested in

developing bioassay systems outside their own

area of interest. Even though a program is

designed to identify only one or two types of

Table 2.—information To Be Included in a Data Base

for Drug Development From Plants

Plant characteristics: Latin binomial effects claimed;

common names; place of collection; geographic

range; parts of the plant studied.

Ethnomedical uses: Crude plant material or type of

extract used to prepare the dose; dose employed,

administration, and dosage regimen; beneficial effects

claimed; side effects reported.

Chemical constituents: Part of plant in which specific

constituent is present; range of percentage yield of

the chemical; data on seasonal or other variations in

chemical quality or quantity.

Experimental testing: Type of solvent used to prepare

extract; type of test (in vitro, in vivo, human study);

test species (e.g., rodent, primate) and status; dose

and route of administration.

Other information: References to compounds that have

been partially or completely synthesized; studies of

cultivation; effects of cultivation, processing, and

storage on yield of useful active constituents.

SOURCE: Office of Technology Assessment.

24-503 0 - 83 - 4
42 ● p/ants: The Potent/a/s for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

biological activity, it would be cost-ineffective

not to carry out as many bioassays as possible.

Routine techniques are available for isolation

and purification of active principles after bioassay-directed plant fractionation to enrich the

biological activity; however, most existing compounds could not be separated economically

from plants using the more sophisticated procedures. Efforts should be made to use simplified procedures so that high extraction costs

do not prevent commercial development. Clinical evaluation is expensive and complicated,

requiring evaluation at several stages by FDA.

The estimated total cost for developing a new

drug depends on the costs for clinical testing,

but would fall between $5 million and $35 million.

Ten computerized online data bases have information useful to a plant-derived drug development program (table 3). All but one are unable to compare, correlate, or analyze research

data analytically; they are solely bibliographic. Ideally, one would desire a nonbibliographic

file that could list and, by computer, compare

or correlate real data contained in pertinent

citations, then present the data in a digestible

tabular form providing the citation sources. In

1975, NAPRALERT (Natural Products Alert)

was initiated to overcome the difficulties in

using existing files for developing research

projects associated with natural products and

drug development.

Approximately one-third of the citations now

computerized in NAPRALERT represent retrospective searches of literature from the early

1900’s to the present. The remainder cover current information. In addition to bibliographic

information, NAPRALERT records the chemical constituents and pharmacological bioassay

information from plant, microbial, and animal

extracts. The accepted and synonymous nomenclature of the organism, the parts of the

organism used in the study, and the geographic

source of the material are important elements

of the data base. NAPRALERT also records

ethnomedical or folkloric notes as they are encountered in the literature.

This data base can be used to systematize

random screening of plants through organized

computer search and analysis of data to proTable 3.—Data Bases Pertinent to Drug Development

Name Developer Contents

Agricola

BIOSIS

PREVIEWS

CAB

FSTA

CACON

MEDLINE

IMEPLAM

—

USDA

Biosciences

Information

Services

Commonwealth

Agricultural Bureau

of England

Food Sciences and

Technology

Abstract

Cacon Chemical

Abstracts

Condensate

National Library of

Medicine

Mexican Institute

for the Study of

Medicinal Plants

Chinese University

Agricultural chemistry and engineering, food and plant science, nutrition and related agricultural fields

Life science for microbiology, plant and animal sciences, experimental medicines, agriculture, ecology, pharmacology, biochemistry, biophysics

Compilation of 20 agricultural science data bases; includes plant and animal breeding

abstracts, plant pathology, nutrition, entomology, related fields

Agricultural chemistry, food science, home economics, patents

Most life sciences and physical sciences

Life sciences and/or medical information

Natural history and folkloric claims for Mexican plants

Retrospective and current literature citations and brief abstracts of Chinese publications

of Hong Kong on traditional medical practices

NAPRALERT University of Illinois Bibliographic information; chemical constituents; pharmacological bioassay information;

plant names, parts and geographic source; ethnomedical information

SOURCE: Office of Technology Assessment.
Ill.—Summary and Discussion of Each Workshop Paper ● 43

vide a ranked list of the more probable candidates for study. Such a method using

NAPRALERT was tested for a WHO Task

Force assembled to identify indigenous plants

potentially useful for human fertility regulation, identifying approximately 4,500 plants

based on folkloric claims or laboratory experiments. Three hundred were identified as

most promising for study through folklore information, pharmacological, and geographic

data. Fifty have received preliminary laboratory investigation, and eight have confirmed

activity but have not undergone clinical testing

yet.

NAPRALERT has the capability to present

in one computerized report all published information on folklore uses, biological activities

(in vitro, in animals or humans), and chemical

constituents. Together these data may suggest

areas for research on new uses or applications

of a specified plant or group of plants. They

can also be used effectively to assess potential

dangers or to suggest safeguards that should

be employed when using certain plants.

While plants already are important ingredients of U.S. pharmaceuticals, they could be

potential sources of many new chemicals for

the drug industry. Despite this potential, pharmaceutical companies have discontinued

plant-drug development programs. One reason

they give for their disinterest is the high cost

of developing a new drug. Any means of systematizing plant selection for screening by making data on past research and folklore use readily available would decrease research time and

improve the chances of discovering a marketable drug. Ten automated data bases exist that

can provide such information useful to drug

development programs. NAPRALERT is the

only nonbibliographic file and represents a

unique data retrieval system of great potential

value to drug development work.

USDA'S DATA BASE ON MINOR ECONOMIC PLANTS

The world has thousands of minor economic

plant species which potentially are as important ecologically and economically as the dozen major agricultural species. There is an overwhelming number of climatological, pedological, anthropological, latitudinal, and biological variables associated with these minor species. The Economic Botany Laboratory (EBL)

of USDA is trying to gather such data on these

potentially useful species.

Seven data base files and their subsets are

or have been online, and three prototype files

have been developed. The online files can be

linked to each other through scientific names

to provide more complete information of species’ characteristics. But funding has declined

for this service in recent years; some files have

been taken offline and others have ceased to

grow with increases in available information.

Data Base Files

Ecosystematic File incorporates data from

over 1,000 questionnaires mailed worldwide to

scientists and extension people, intentionally

emphasizing developing countries. Within 2

years some 500 people responded, sending published and unpublished ecosystematic data (annual rainfall, annual temperature, soil type, soil

pH, elevation, etc.) on 1,000 species of economic plants, weeds, and nitrogen-fixing species.

Each species in the file is recorded with the

name and address of the reporting scientist(s),

thus providing opportunities for more specific

followup.

Yield File includes data from the questionnaires and from publications of experiment stations. The entries probably account for less

than 1 percent of the yield data published an-
44 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

nually by experiment stations. With increased

funding, the data in this file could be increased,

thus providing a means to compare yields of

exotic crops (with various inputs) in ecologically similar areas.

Climate File includes monthly temperature

and rainfall means for about 20,000 stations

worldwide and the elevation of most of these

localities. This file is the computer tape of

Wernstedt’s World Climatic Data, supplemented by information from publications and

the questionnaire sent out by USDA. A continentality variable that compensates for seasonal temperature extremes of continental sites

has been added to the file. This helps differentiate among climates with similar mean annual

temperatures but different vegetational potential. A species’ ecological amplitude can be

determined by using this file in conjunction

with ecological data for geographical areas

from which the species is reported.

Where no data on climate are available, the

presence of weed or plants with known ecological amplitudes of temperatures and rainfall can help predict climate in remote areas.

Data on weeds’ climatic amplitudes were

added to this file under the Ecological Amplitudes of Weeds program. Another use of the

Ecological Amplitudes of Weeds program is in

mapping the potential for an alien weed to

spread in the United States. Climates favorable

to the spread of a weed can be located by determining ecological amplitudes of a weed

through consulting its distribution and extracting climatic data from the Climate File.

EBL has formulas for converting its 20,000

climatic data sites into Holdridge life-zone

maps for countries not now mapped in the

Holdridge system. Standing biomass, total carbon, and annual productivity of the zonal forests can be projected from this information,

giving real or projected yield figures for highbiomass grasses, energy-tree plantations, or

conventional crops. This could provide some

guidelines for choosing the best crop-agroforestry combinations for agricultural development in Third World countries.

Nutrition File includes at least one credible

entry for each plant species in Food Composition Tables for East Asia, Africa, and Latin

America. The plant’s nutritive contents (elements, vitamins, calorie, and fiber content) are

ranked extremely low, low, high, or very high

relative to USDA’s recommended dietary allowance (RDA). The Nutrition File (as-purchased proximate analysis or zero-moisture

analysis) can be linked through a species’ scientific name to the Yield File to convert yields

of grain per hectare to yields of protein per hectare, and to the Ecosystematic File to show

which will yield the most leaf protein per hectare under any specified combination of annual

temperature, annual precipitation, soil pH, etc.

Ethnomed File was compiled to encourage

Third World countries to supply medicinal and

poisonous plants for a collaborative screening

program with the U.S. National Cancer Institute. With 88,000 entries, the Ethnomed File

is probably the largest extant computerized

data base for folk cancer remedies. The file also

covers general folk remedies and pesticidal activities. Ethnomed no longer is online but survives as a much consulted printout.

Prototype Data Bases

Agroforestry File includes different subfiles

containing information on ecological parameters, germination requirements, nutrition values, cultural requirements, yields, wood characteristics, use, and plant pathology for several

species considered for agroforestry. Perhaps

the prototype file’s greatest impact was to show

that almost no data were available on most nonconventional economic plants.

Pest file has only about 2,500 entries listing

the scientific name of the host plant, the plant

part affected by the disease of insect, and the

name and type of pest. Although this information is useful for predicting pest problems if

the pest is known to be in the area chosen for

introduction, it does not help predict the possible presence of the pest on the site. If the file

were expanded to provide data on the ecolog-
Ill.—Summary and Discussion of Each Workshop Paper Ž 45

ical amplitudes of pests and diseases, it could

help avoid or reduce the risk from pathogens

or pests. This could launch a new phase in biological control of pests’ “biological evasion.”

For example, where the host tolerated more

cold than the pests, planting in the colder area

might be advantageous.

Intercropping lists major and minor crop

combinations, all species in pasture mixes,

yield data, yield differentials, and cultural and

other variables. By using the scientific names

to link this and other files one could find out

which crops have been tried around the world

as intercrops. In densely populated Third

World areas, intercropping clearly promises

more quality, quantity, and/or variety of crops

per hectare than monocropping.

Limitations to the application of the EBL data

compilation program exist. In intermediate

ecotypes, the effects of factors such as slope,

soil porosity, soil type, vegetation cover, cultural conditions, insolation, prevailing winds,

etc., on plant characteristics maybe significant.

Few data are available and some of these

variables are entered for only a few places. The

20,000 sites for which there is climatic data are

not classified under a single soil-classification

system. This prevents correlation of plants’

ecological tolerances based on soil properties.

A major program would be needed to collate

the Food and Agriculture Organization and/or

USDA soil units with the 20,000 climatic data

sites, soil pH, weeds, crops, yields, diseases,

insect pests, and native perennials. This could

be done for a large number of the 20,000 sites.

This “International Plant Utilization Data

Base” would develop ecological amplitudes

and means and determine optimal conditions

for all the economic species of the world and

their pests and pathogens. Ancillary to this

could be the development of an economic data

base that includes transportation costs, shelf

life, world demand, trends in production, and

current price of a species. Crops that make the

most sense economically then could be chosen

from the many crops ecologically adapted to

the area. Experimental data resulting from

trials would be used to select the right species

for that particular area and to augment and refine the data base. This capability of matching

crops to their most suitable environment would

be extremely valuable for use in both the

United States and in developing countries. It

would assist significantly in agricultural planning programs sponsored by international development agencies by suggesting best crop options for target environments. Use of the EBL

data base could minimize crop-development efforts in environments that are marginal or unsuited to the crop species and help avoid or

reduce the use of costly or ecologically disruptive agricultural inputs (e.g., energy, water,

agricultural chemicals). In addition, it could

help reduce the risk of spread of disease and

pests.

Such a data base could select species best

adapted to a given climate for whole-plant utilization schemes in which food, oilseeds, leafproteins, chemurgics, drugs, etc., would be the

main products and biomass would be an energy-producing or commercial fiber byproduct.

Greater plant use becomes more important as

petroleum supplies—for energy and for transportation of products—become more scarce

and expensive.

Without renewed funding these data bases

have a short life expectancy. The cost of maintaining the files online is at least $10,000 a year

before any programs are run on the data.

USDA is a constant user; daily, scientists consult the hard copy generated by the EBL data

base to answer questions on agronomy, agroforestry, climate, ecology, ethnomedicine, nutrition, pathology, and utilization. Many other

U.S. Government agencies have benefitted

from the files and could reduce future costs by

consulting them.
—
IV ●

Findings and Discussion

OPPORTUNITIES

The potential for developing new sources of

valuable plant chemicals is largely unexplored

and the benefits from doing so unexploited. Of

the Earth’s estimated 500,000 to 750,000 species of higher plants, no more than 10 percent

have been examined even cursorily for their

chemical makeup. An even smaller number are

grown commercially: only about 300 plant species worldwide and 100 species in the United

States have been developed as crops for food

and fiber products. In concentrating on a relatively few crops, other plants that could

become important food and nonfood crops

have been neglected. Plants are known sources

of medicines, proteins, waxes, oils, resins, tannins, and other useful substances, Technologies to extract these chemicals are becoming

more advanced, and developed whole-plant

utilization schemes in which these substances

are extracted and the residue used as a commercial byproduct or for energy production are

receiving increased attention. Developing new

crops and industries based on plant extracts

and extraction residues provides opportunities

for agricultural and industrial expansion that

could benefit farmers, consumers, industry,

and the Nation as a whole. New-crop and plantproduct development could:

●

●

●

●

●

●

●

●

●

diversify and increase efficiency of agricultural production,

improve and possibly expand land resource use,

offer increased economic stability to farmers,

create new and improve existing agriculturally related industries,

increase employment opportunities,

provide consumers with new products,

provide industries with alternative sources

of raw materials,

help supply the country with strategic and

essential materials, and

improve the Nation’s balance of payments

through import substitution.

Some of the greatest benefits of new-crop development would result from crop diversification. As already pointed out, the U.S. agricultural system is based on a limited number of

crops. Because agricultural research and development efforts on these crops have contributed to their increased productivity, over-production has become a regular feature of American agriculture. Federal price support programs and production limitation programs designed to protect farmers from depressed commodity prices are costly. The Congressional

Budget Office predicts that agricultural price

support programs will cost the Federal Government at least $21 billion in 1983 alone. Alternative crops could help shift production away

from traditional crops and into new crops, thus

increasing economic opportunities for farmers

and reducing Federal farm-support programs.

The concentration of U.S. agriculture on a

small number of major crops invites economic

instability. The economies of many agricultural

areas are based on one or a few crops commonly grown in monoculture, leaving farmers vulnerable to the effects of pests and changing

market conditions. New crops could provide

alternatives to traditional crops and opportunities to develop new agronomic systems such

as multiple-cropping or intercropping. Production of two or more crops offers an economic

buffer in the event that one of the crops fails

or the market price drops. In addition, the development of whole-plant utilization schemes

in which many commercial products are available from one crop offers farmers greater economic insurance against price fluctuations

than if they depended on a single product from

a crop.

Widening the crop base also would enable

the farmer to choose a plant species best suited

to local agronomic conditions. U.S. agriculture

has been largely manipulative; farmers have

modified the land resources to conform to a

49
50 ● Plants: The Potent/a/s for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

particular crop. An improved match of crop

and resources could help reduce increasingly

expensive and scarce inputs of energy, chemicals, and water. For example, assuming that

markets for its products can be successfully

developed, milkweed, a semiarid-land plant, is

a potential substitute for irrigated crops now

grown in the western Great Plains where

ground water resources are being depleted.

Similarly, crambe, another dryland crop, might

be more effectively grown than corn or wheat

in dry areas marginal for these crops. Plants

ecologically adapted to a site might require

smaller inputs of pesticides than crops without

built-in chemical or biological defenses against

local pests.

Widening the crop base might also increase

U.S. cropland acreage. If developed, new crops

that could be cultivated on marginal lands

without large amounts of chemicals, fertilizers,

and irrigation water offer the opportunity to

extend production to these lands that are unable to support traditional crops. Plants that

might be cultivated on arid lands, in areas

where the soils are highly alkaline, and on

reclaimed strip-mined lands should be investigated. Benefits resulting from cultivating such

lands include increased farming opportunities

and stimulation of industrial production in

economically depressed areas.

New crops could provide the consumer with

a wide range of new products, including medicines; essential oils for cosmetics, spices, and

drugs; detergents; vegetable dyestuffs; and insecticides, to name a few. One striking example of new plant-derived products is the highly

effective anticancer drugs extracted from the

Madagascar periwinkle (Catharanthus roseus)

plant. The ended plant (Phytolacca dodecandra), which contains a potent molluscicide, is

another example of a plant that may provide

great human health benefits. Although it is still

being tested, this molluscicide might prove to

be important in the control of schistosomiasis,

a tropical/subtropical disease affecting zoo million to 300 million people.

Plant-derived insect toxicants, repellents, attractants, and various biocidal compounds constitute another important group of extracts

with potential commercial value. These plant

extracts offer alternatives to some synthetic

compounds that have negative and long-lasting ecological impacts on the environments in

which they are applied. A variety of these natural biocides can be extracted from arid- and

semiarid-land plants, including neem tree,

sweet basil, and sagebrush. Producing such

crops could improve or extend cultivation to

lands that are often unproductive for U.S. food

and fiber crops. These products could be particularly effective for pest control where other

arid/semiarid-land plants are being cultivated.

Just as arid/semiarid-land species represent

a group of plants with largely unexplored

production and product possibilities, marine

plants have been relatively untapped as sources

of commercial products. Except for extracting

agar, carrageenan, and alginate for the food industry, little commercial processing of marine

algae is done in the United States. Research in

the relatively new field of marine photochemistry has revealed that marine algae are sources

of unique chemical compounds. Certain marine algae show potential as sources of pharmaceuticals, agricultural chemicals, food and

food products, enzymes, and chemical feedstocks. Multiple-product development seems

promising. With improved mass culture techniques, large-scale production of algae in the

ocean and in controlled coastal facilities may

be feasible. Development of marine algae for

commercial products provides new opportunities to expand the U.S. production base and

develop related industries.

New crops could be sources of industrial raw

materials such as oils, waxes, gums, fibers, and

chemical feedstocks. These raw materials

could stimulate the development of new industries and enable existing firms to expand their

product lines. Because many of the plants being researched would be cultivated on marginal lands, resulting industrial expansion would

occur in places that commonly are economically depressed. These industries could stimulate

local employment opportunities not only in the

agricultural but in the industrial sector.

Domestic production of plant-derived chemicals could have a beneficial economic impact
IV.—Findings and Discussion . 51

through import substitution. The United States

imported an estimated $23 billion worth of

agriculturally produced industrial materials

and petroleum for industrial feedstocks in

1979. Domestic crops that could provide direct

substitutes for agricultural products or alternative chemicals to petroleum as fuel or industrial feedstocks conceivably would be important in import substitution and for foreign exchange savings.

Domestic production of substances considered strategically important to the Nation or

essential to U.S. industry should be encouraged. There are obvious advantages in promoting self-sufficiency, guaranteeing a ready supply, avoiding stockpiling, and reducing reliance on stockpiled materials. Research is being carried out on plants that can serve as

sources of industrial and strategic materials

and as petroleum substitutes. Certain materials

of national strategic importance are required

by law to be stockpiled. Listed among strategic

materials are castor oil, an important industrial

coating and lubricant; sperm whale oil, a heatresistant liquid wax whose primary strategic

use is as a lubricant in jet engines; and rubber.

Half the rubber used in the United States is

synthetic; the remainder is natural Hevea rubber. The United States imports all its natural

rubber at an annual expenditure of $1 billion,

making rubber the Nation’s second-mostexpensive import after oil. The United States

could reduce significantly its dependence on

foreign sources of rubber by producing it domestically. Because of its importance to the

military, the Federal Government is funding research on guayule, a desert plant that is a promising substitute for Hevea rubber. Guayule is

being studied as a potential crop and is being

grown on small commercial acreages in the

Southwest. *

Jojoba (Simmondsia chinensis), also in limited commercial production in the United

States (about 20,000 acres), is a potential sub-

*Guayule was grown in the Southwest United States during

World War II as a substitute source of natural rubber when imports were cut off. After synthetic rubber was developed and

Hevea rubber trade was restored after the war, production of

guayule in the United States was discontinued.

stitute for sperm whale oil. Use and importation of sperm whale oil was banned in the

United States in 1970 under the Endangered

Species Act. Another possible substitute for

sperm whale oil is a chemical extracted from

meadowfoam (Limnanthes douglasii), now being studied at the Department of Crop Science

at Oregon State University. Limnanthes oil can

be converted to a liquid wax that has properties similar to jojoba oil.

Castor oil is extracted from castor beans

grown in Brazil. Although castor beans have

been produced in the United States, a substitute

oil is being sought because castor beans have

toxic and allergenic properties that are hazardous to humans and animals and pose waste-disposal problems. A possible substitute oil can

be obtained from Lesquerella species, members

of the cabbage family that can be grown in the

United States.

U.S. stockpiles of natural rubber and castor

oil are far below the level required by law. Acquiring, maintaining, and storing these strategic stockpiles would cost the United States an

estimated $1.1 billion (in 1979 dollars) by 2000.

Domestic production of substitutes could help

eliminate the need to stockpile natural rubber

and castor oil.

The United States depends on other countries to supply a major portion of its demand

for petroleum. The interest of the U.S. Government and the chemical industry in domestic

production of plants for fuel and chemical feedstocks has increased as a result of the rise in

petroleum prices since the 1973-74 Arab oil embargo. Researchers at the USDA Northern Regional Research Laboratory in Peoria, 111., are

investigating several plants as potential petroleum substitutes. Oils or fatty acids from seeds

of certain plants may provide substitutes for

petroleum-derived chemicals and some botanochemicals. New oilseed crops are found at a

variety of stages of development. Preliminary

chemical and botanical investigations have indicated crop potential of Cupea species as

sources of lubricants and detergents, Veronica

species and Stoke’s aster (Stokesia laevis) for

manufacture of industrial coatings and plastics, and Lesquerella species as sources of sub-
52 . Plants: The Potentials for Extracting protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

stitutes for castor oil. More extensive basic and

applied research has been carried out on two

other promising species: meadowfoam and

Chinese tallow tree (Sapium sebiferum). Small

amounts of jojoba (about 20,000 acres) and

crambe (Crambe abyssinica) are further along

in their development as new crops; they are being grown commercially on small scales.

Fuel crops under study fall into four categories: oilseeds, hydrocarbon crops, starch/sugar

crops, and biomass plants. Oilseeds could provide diesel fuel; hydrocarbon extracts could be

cracked to produce gasoline or liquid fuels;

starch/sugar crops are used in alcohol production; and biomass crops could undergo alcohol

fermentation, gasification, or direct burning. *

Research funding available through USDA,

the Department of Energy, and the National

Science Foundation (NSF) has supported work

on milkweed (Asclepias spp.), buffalo gourd

(Cucurbita foetidissima), and gopher plant

(Euphorbia lathyris) as potential energy crops.

Because these and other potential fuel crops

could be grown on arid or semiarid lands, they

would not compete with food and fiber crops

for prime agricultural land. Further technologi-

*For more information see OTA 1980 report Energy From

Biological Processes, and OTA 1979 technical memorandum on

gasohol.

cal, ecologic, and economic analyses are

needed before these plants could be developed

as commercial sources of fuel.

In summary, the development of new crops

for plant extracts offers many potential social,

economic, and ecologic benefits on both local

and national levels. New-crop development

could benefit agriculture through crop diversification, expansion of the land resource base,

and increased efficiency of crop production

(e.g., rotation and multiple-cropping systems);

industry through product diversification and

raw material availability; consumers through

provision of new products and increased employment opportunities (on-farm and industrial); and the Nation through reduction of agricultural price support programs, import substitution, and independence from foreign

sources of strategic and essential industrial materials.

Successful introduction and establishment of

a crop, however, require a long and adequately funded period of coordinated R&D. Each

potential crop would be faced with a unique

set of technical and economic constraints that

could threaten its commercial development.

The field of new-crop and plant-product development on the whole faces some general constraints. These will be discussed below.

CONSTRAINTS TO NEW CROP DEVELOPMENT

Potential crops require many years of agronomic research and product development balanced with market development for successful

introduction. This involves a long chain of

R&D steps including selection of plant species

(involving chemical and biological characterization); isolation and purification of desired

compounds; crop development (including genetic improvement, agronomic research, and

harvesting technologies); transportation and

storage; processing technologies; and marketing. (Plant-derived pharmaceuticals, biocides

—e.g., insecticides, fungicides—and foods for

human consumption–e.g., proteins, vegetable

oils—require additional research because before marketing they must be tested in compliance with FDA regulations to ensure that they

present no health or environmental hazards.

Clinical testing for pharmaceuticals is particularly expensive and time-consuming.) Once

a product is marketed, further research on agricultural practices, processing, and marketing

would be required to fine-tune on-farm and industrial techniques. The future of new-crop

development for plant extracts will depend on

the existence of appropriate R&D systems that

can facilitate breakthroughs and continued improvements.
IV.—Findings and Discussion ● 53

Many constraints to developing new crops

and plant extracts industries are encountered

at the four major steps in the development

process—namely:

● research,

● crop production,

● industrial processing, and

● marketing.

The following discussion examines problems

and potential impacts of new-crop/plant-product development at each stage.

Research

Developing a new plant-extract industry requires research in a number of disciplines, including chemistry, botany, genetics, agronomy,

entomology, engineering, and marketing. Expertise in all these fields is rarely concentrated

in one institution. For example, most agronomy research is carried out in public, landgrant institution, and USDA, whereas industrial biochemistry and engineering expertise is

primarily found in the private sector. Both the

private and public sectors depend on the foundation of basic science provided by university

researchers. Clearly, coordination of research

efforts of Federal and State Governments, universities, and industry is essential if new crops

and plant extract products are to be developed

efficiently.

Agricultural research in the past has focused

on improving yields of existing U.S. crops or

on crop improvement of introduced plants.

Only within the last decade has much effort

been directed toward developing new crops for

plant extracts in the United States. Although

scattered plant screening and crop development projects in the United States have demonstrated the potential for crop and product

diversification, work in this field and support

for it remain limited and sporadic. The limited

attention of industry is focused mainly on

industrial feedstocks. Industry’s lack of interest

in plant-derived pharmaceuticals is notable.

Funding for new-crop development is only

a small portion of USDA’s research budget,

Combined State and Federal (USDA) appropriations for agricultural research in 1983 total

about $1 billion, most of which will be spent

on the country’s well-established crops. The

share of new crop research within USDA’s

Agricultural Research Service (ARS) is only $3

million this year. * An estimated additional $3

million to $4 million is being spent this year

on such research by NSF and other Federal

agencies. When research funding is cut, work

on new crops often sustains the heaviest budget

reductions, losing out to established crops.

Ironically, while research on new crops, which

offers opportunities for crop diversification

and new markets, remains underfunded, the

costs for Government price-support programs

for overproduced crops continue to expand,

Recent cuts in Federal support for applied

research have been made on the premise that

the private sector should play a larger role in

applied research, freeing public moneys for basic research. At the same time, however, nondefense Federal agency research budgets and

appropriations for universities and competitive

grant programs, particularly in the life sciences, have been cut, reducing support for

basic research.

If the private sector is to play a larger role

in research, it must be both able and willing

to invest. Within the private sector, venture

capital and multinational corporations are

most likely to take the initiative in developing

new plant products. Multinationals with wellestablished research branches might be able to

expand research efforts to fill gaps in basic

research left by Federal cutbacks in research.

The private sector, however, tends to wait until enough basic and applied research has been

done to demonstrate profit potential before investing in further research. Once profit potential is established, the private sector becomes

much more willing to invest in product R&D.

*ARS research on new crops was carried out in Phoenix, Ariz.;

Pasadena, Calif.; Bryon, Ga.; Tifton, Ga.; Peoria, Ill.; Ames, Iowa;

Be]tsvi]]e, Md.; East Lansing, Mich.; Mayaguez, P. R.; and Lubbock, Tex. The total funding for these research efforts was $2.79

million in 1982, $2.95 mil]ion in 1983, and is projected to be $2.95

million in 1984. (James T. Hall, Executive Secretary for USDA

Research and Education Committee, personal communication,

May 1983.)
54 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

The process, however, depends on a foundation of basic research. It appears that the public

sector must provide leadership by laying the

foundation for new crops. Historically, the development of the existing U.S. crops has depended on substantial Federal and State support; new crops will not be exceptions. *

New-crop development will depend on a certain amount of agronomic research carried out

by ARS and State Agricultural Experiment Stations (SAES) and perhaps DOE (energy crops),

Department of Defense (strategic crops), and

Department of Commerce (marine plants). At

the same time, however, funding for plant extracts work should be made available through

competitive grants programs administered by

USDA and other appropriate Government

agencies. USDA is authorized under the Food

and Agriculture Act of 1981 to conduct a competitive grants program on new crops. Not only

is this an efficient way to match research needs

with expertise but it reduces pressures within

the agencies to maintain or increase traditional

crops research at the expense of new-crop development.

Federal funding for new crops and plant extracts work is also available from NSF. NSF

grants, however, generally are provided for basic scientific research, not for much needed applied research and development. For example,

in the pharmaceutical area, funds are available

for biochemical screening but rarely for followon research needed for drug development. NSF

recently launched a new Small Business Grant

program, but it specifically excludes grants for

product development work. Bridging the gaps

between basic and applied research and between research and product development is

one of the major obstacles to new-crop development.

In addition to providing basic research and

funding, the Government could be instrumental in stimulating private sector involvement

in plant extracts by offering economic incentives for industry to invest in plant products.

*For more information see OTA technical memorandum,

“Agricultural Postharvest Technology and Marketing Economics

Research,” April 1983.

Given current economic conditions (e.g., recession, high-interest rates), a critical problem for

the plant extracts industry will be how to leverage public and private funds for R&D so companies will be neither inappropriately subsidized nor discouraged from entering the industry. In addition to providing publicly funded

“front-end” research, the Federal Government

may need to provide other incentives such as

tax benefits and low-interest loans to stimulate

private interest in plant-extracts production.

Such incentive systems must meet the needs

of the companies, whether venture-capital

firms, small businesses, or multinational corporations. Mechanisms available to the Government to encourage new-crop development

and shifts in production should be examined.

One reason cited for industry’s general disinterest in the plant extracts field, especially

in plant-based pharmaceuticals, is uncertainties of patent protection. There seems to be

some uncertainty about the patentability of different kinds of products and processes. In addition, some companies claim that they do not

invest in natural-product development because

it is difficult to obtain a product patent and

because a processing patent, which is easier

to obtain, does not offer sufficient protection

against competitors. Industry also shows some

hesitation to invest in research protected under

a publicly owned patent. A risk exists that a

competitor will use the Freedom of Information Act (FOIA) to obtain proprietary information on work done in an area protected by a

public patent. Various agencies treat the FOIA

differently; some will allow the sponsoring

company to black out items of proprietary interest before information is made available;

others will not. A related problem raises if a

product or technique is developed in a Statesupported institution; the sponsoring company

cannot be given an exclusive license for it. The

sponsor may be assured first right of refusal

but the percentage return on sales must be

negotiated, a time-consuming task that university scientists are apt to avoid. Another patentrelated disincentive to industry’s investment

in plant extracts is specific to pharmaceutical

companies. The length of a pharmaceutical patent (17 years) includes the time necessary for
IV.—Findings and Discussion ● 5 5

clinical testing, thus reducing the time the

product is on the market and protected by the

patent. Patent laws should be investigated in

relation to plant extracts, and modifications to

those laws to offer improved protection to companies investing in certain plant extracts work.

In summary, potential Government roles in

encouraging new plant-product development

include the following:

1.

2.

3.

4.

provide SAES, ARS, or other Federal agency funding to nongovernment research

bodies for R&D;

provide other incentives or eliminate disincentives in order to encourage private

sector R&D;

carry out research itself in areas deliberately avoided by the private sector, when

it is against the public interest to have

research results protected by proprietary

interest, and where public research would

stimulate increased private investment;

and

improve coordination of public research

with the technical needs “of industry.

Academia is a vital component of plant extracts work. Land-grant institutions provide expertise in agronomy and postharvest technology whereas other universities are relied on for

advances in basic sciences (e.g., biochemistry,

pharmacology, genetic engineering). While the

public and private sectors depend on academic

institutions for research advances, universities

in turn rely on funding from public and private

sectors. As a result of the intense international

technological competition of the last half

decade, many people feel that public research

should be coordinated better with the technical

needs of industry. One way to foster improved

communication is through cooperative arrangements between industry and universities.

Some such arrangements have been developed

recently in the plant extracts area (e.g., General

Foods Corp. and LPI for tobacco protein research, Procter and Gamble Co. and Oregon

State University for cuphea research), but in

general, the industry-academia link is strained

by the question of proprietary interest. Research findings of universities are usually

assumed to be available to the public. However,

industry may be unwilling to support university research without some chance of long-term

gain provided by proprietary rights to research

findings. This raises concern about corporate

influence on academic research topics and

scholarly communication. While university

scientists are concerned about limitations imposed by patenting, licensing, and need for

secrecy about research findings, industry

seems concerned over the lack of exclusive

license for the product or process. In addition,

some farmers have expressed opposition to

funding by large corporations of agricultural

research at universities for fear it will increase

even further agroindustry’s competitive advantage over small-farm operators or cutoff their

access to much needed information. These limitations and conflicts must be resolved to

facilitate industry-academia cooperation in

plant extracts research.

Clearly, close cooperation is needed among

Government, industry, and universities in newcrop development research to bridge the gaps

between basic and applied (both agronomic

and industrial) research. The respective roles

of academia and the private and public sectors

should be examined and public policy should

be directed toward the goal of improving cooperation between universities and commercial enterprises.

Although each potential crop under investigation requires specific research, there are

general research needs in new-crop and plant

product development. A major constraint to

selecting potential new crops is the unavailability of adequate field-screening techniques. Because plants cannot be screened in the field,

large amounts of plant material must be

brought in from the field to the laboratory for

testing. Effective field-screening techniques

would facilitate the discovery of new chemical

compounds, new sources of known chemicals,

and germ plasm for crop improvement and genetic engineering.

Research efforts involving chemical screening of plants often have been product- or activity-specific; the focus has been on finding

particular chemicals or biological activities.

For example, the National Cancer Institute’s

plant-screening program examined 35,000

plants for antitumor activity but made no systematic effort to record other biological activity
56 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

observed. Plants tested by the program might

not have exhibited antitumor activity but may

have had other useful medical properties. Just

as multiple-product development is cost effective, so is comprehensive screening. Improved

communication and collaboration among research institutions would reduce duplication

and encourage the development of advanced

testing and screening technologies.

Crop Production

The needs and impacts of cultivating new

crops, of course, depend on demand for the

crop and the land area put into cultivation.

Low-demand, high-price “specialty” crops

such as the Madagascar periwinkle would require little acreage, so their impact on existing

land-use patterns would be minimal. In contrast, new high-demand, high-volume crops

such as hydrocarbon and leaf protein crops

probably would have substantial impacts on

the quantity and quality of national land resources. The following discussion refers to

high-volume crops.

Land availability for new high-volume crops

must be carefully assessed. Many such crops

under study, including milkweed, jojoba,

guayule, and crambe, are arid-or semiarid-land

plants that thrive on lands marginal for traditional food and fiber crops. On these marginal

lands, the decision to shift to a new crop will

be largely an economic one and will be made

as markets develop. Converting uncultivated

arid and semiarid lands, both private and public, however, may be more difficult. Efforts to

convert this land to effective cropland may well

conflict with other uses such as grazing or

recreation and involve complex property transfers.

While the decision of a farmer to shift production to a new crop is ultimately an economic one, the risk of allocating production resources to an unproven crop at first may seem

too high. Even if farmers are assured regular

markets for their products, initially they may

need incentives to risk crop changes. Again,

the Government could play a facilitating role

in working closely with local bankers to ensure

that long-term credit is available to farmers for

new-crop production. Further, the Government

might sponsor applied research on the crop to

overcome farmers’ resistance to it.

Assuming obstacles to allocating land for

new-crop cultivation are overcome, effects on

the quality of the land resources allocated to

a new crop must be evaluated. Although some

new crops would be better adapted ecologically

to certain lands than traditional crops, any

change in land use should be made carefully.

Many arid and semiarid lands, for example, are

highly susceptible to erosion, and unless the

new crops are perennials and soil conservation

techniques are implemented, erosion on previously uncultivated lands may degrade the

land resource. New cropping patterns, such as

multiple-cropping, may prevent such damage.

Introducing a new crop may create pest and

disease problems; new plants could introduce

new pathogens or pests to an area or be susceptible to unforseen pest problems themselves. Many of the problems encountered with

new-crop production are the same as those of

traditional crops. But because new crops may

change land-use patterns on marginal lands,

which are more likely to be susceptible to ecological disruption, their impacts on the land

base may be more pronounced.

Industrial Processing

The most serious technical constraints to

new-crop development probably will occur at

the product-processing stage. Processing technologies that appear feasible at the pilot level

often encounter difficulties when scaled-up to

commercial production. For example, although

tobacco protein extraction seems technically

promising at the pilot stage of development,

technical problems with handling plant material, waste disposal, and solvent recovery are

foreseen in commercial production. Commercial production also requires that plant capacity be fully used. Unless crop production is

possible year-round, storage of the plant material will be necessary. When the quality of

a major commercial plant chemical deteriorates rapidly after harvest (e.g., in leaf proteins,
IV.—Findings and Discussion • 57

milkweed), processing must be coordinated

with plant harvest.

Waste disposal, pollution, and other environmental effects from industrial processing represent another constraint on commercial production of plant extracts. Many extraction

processes require the use of solvents. If these

are not recycled, appropriate liquid-waste-management systems must be developed. Because

waste water from processing for leaf protein

and other plant extracts commonly has a high

biological oxygen demand (BOD), it, too, could

be a source of pollution if not disposed of

carefully. Other environmental concerns associated with extraction are significant as well,

and an economic assessment of plant extract

technologies must factor in such costs.

There may be social costs involved when establishing processing and production facilities

in areas previously economically depressed or

in rural regions. Infrastructure needs, population shifts, inflation, and irregular boom and

bust cycles of development are among the consequences of rapid economic growth. Planning

for financing the front-end costs of development and for allocating resources within the

community must be an integral part of largescale commercial endeavors in plant extracts

industries.

Marketing

Unless a market does or potentially can exist for a plant extract(s), industry probably will

not invest in product development research

and farmers will not invest in crop production.

However, the development of a market depends on farmers’ willingness to produce the

crop and industry’s willingness to invest in

product research and marketing to stimulate

product demand. This “Catch-22” of which

comes first, the product or the market, exists

for all new products but can be particularly

complicated in the plant extracts field where

agriculture and industry must be closely linked.

The timing of markets is critical; marketing

and crop production must be coordinated effectively. If markets are created before production can fulfill demand, buyers can become disinterested and the product’s chance for success

will be impaired. If production exceeds market

demand, farmers will become disillusioned.

Marketing a crop that has specialized uses and

few alternative applications may be difficult

because production must be closely coordinated with very specific markets. Production

and processing of a multiproduct crop must be

coordinated with many markets, which also

may be difficult logistically.

Another marketing problem may arise if a

market exists but well-established products

already fulfill the demand. For example, tobacco protein (Fraction 1) would have to compete

with egg albumin in the food processing sector and with alfalfa in the market for betacarotene. Because both industries—egg albumin and beta-carotene—are well-established,

tobacco probably would have a difficult time

entering the market. Similarly, some of the

products of milkweed (pectin, fiber, livestock

feed) would have to compete in the marketplace with well-established domestic sources

of these goods.

All new crops would need agronomic refining and new products need processing improvements after scale-up to commercial production. In order for farmers and industrial

producers to invest in the crop, however, it

would have to be profitable or perceived to

have commercial potential even before refinements have been made. One way to overcome

this barrier would be to introduce a product

from the crop as a “specialty item.” This highpriced item could make the crop competitive

in the short run with traditional crops and

could act to encourage the crop’s expanded development. The crop could be grown in small

quantities for predictable returns, thus enabling

farmers to solve production problems and providing the time necessary for further agronomic and processing research essential for longterm development of the crop. This leveraging

method is being employed with jojoba. Smallscale commercial production of the plant is

supported by commercial sale in health food

specialty markets (e.g., shampoos, skin creams).

Once crop and product production methods

24-503 0 - 83 - 5
58 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

are refined, jojoba can be cultivated on a much

larger scale for its potential high-demand oil.

Consumer acceptance of the product(s) is, of

course, the most important factor in marketing

success, and sometimes the most unpredictable. Soybean meal has been developed and

produced as a high-quality, low-cost source of

protein for human consumption, but consumers prefer to buy other more expensive proteins. Tobacco leaf protein faces a similar

obstacle. Although technical problems remain,

the LPI process could be scaled-up to commercial production at this time. The overriding

deterrent to commercial production, however,

is producers’ lack of confidence that consumers would accept tobacco protein concentrates

as protein supplements or cigarettes produced

from deproteinized tobacco.

In summary, constraints to new-crop development are many and need to be overcome

from beginning research to final marketing.

Such constraints in research, crop production,

industrial processing, and marketing include:

● research:

— insufficient cooperation among the Federal Government, States, universities,

and industry;

— scant research dollars identified for

such research;

— inadequate linkages between basic and

applied research and product development;

— lack of Federal economic incentives to

increase industry’s involvement;

— inadequate field-screening techniques.

● crop production:

—

—

—

possible major changes in current landuse patterns;

lack of incentives for farmers to take

risks with new crops;

potential adverse environmental impacts of some new crops on the natural

resource base;

● industrial processing:

— the difficulties in scaling-up from pilot

operations to full-scale production;

— waste-disposal problems faced at fullscale commercial production;

● marketing:

— the “Catch 22” of which comes first—

the product or the market?;

– breaking into the market that is already

filled by established products;

— developing consumer acceptance of

new products.

AREAS FOR POSSIBLE CONGRESSIONAL ACTION

The potential for the technological and scientific screening of plants to find the new useful substances they contain has barely been

tapped. Research to date strongly suggests that

this is a promising field that could provide

wide-ranging benefits to the United States in

the near and far term, especially if nonrenewable fossil fuel resources climb in cost. To date,

no more than an estimated 10 percent of the

world’s 500,000 to 750,000 higher plant species

have been screened for their chemical makeup

even in a cursory manner. Nevertheless, the array of useful and important products extracted

from plants is impressive.

Today, a worldwide concern exists among

scientists that plant materials as yet unscreened

are being lost before their potential value is

determined. Loss of genetic plant materials

probably is greatest in the Tropics where pressures to clear vegetated land for agriculture to

feed rapidly growing populations are extremely

heavy. (See OTA report entitled Technologies

To Sustain Tropical Forest Resources.)

Discussions of the experts assembled by OTA

reflected a need for the United States to address the issues and problems above in a timely

fashion. Because of the rate of land-clearing

worldwide, society may no longer be able to

afford the luxury of postponing action to some

far distant date. Three opportunities for possible congressional action emerged from this exploratory activity:

● develop a coordinated, comprehensive

plan involving the Government, industry,
IV.—Findings and Discussion ● 5 9

and universities to screen plants, assess

new chemical resources from the plants,

and foster their commercial development;

● assure adequate funding for Government,

university, and industry research into

plant screening for the extraction of commercially valuable substances and for crop

and product development;

. provide incentives (e.g., tax benefits, subsidies) or minimize disincentives (e.g., uncertainties in patent laws) so as to encourage research by industry on new crops for

chemical extracts; and

● encourage bilateral and multilateral agreements for cooperative research and evaluation of untested species.

No coordinated, comprehensive U.S. plan involving the Government, industry, and universities exists for: 1) screening U.S. or foreign

plants for their natural chemical components,

2) determining the nature and possible uses for

the natural plant chemicals they may contain,

and 3) fostering development of such new

crops and their commercialization. Scattered

efforts are under way in the United States to

deal with some of these needs but the total effort is small. Traditional major food and fiber

crops have strong agricultural lobbies behind

them that work hard to maintain Federal and

State Government attention and research. Potential new crops and chemical-screening efforts lack the support of similar strong lobbies.

Industry generally focuses on deriving benefits

from their research over the short term. It is

unlikely, therefore, that they would undertake

a broad-based, long-term analysis of the

thousands of plants as yet unstudied. In addition, vertically integrated, very large food industries concentrate mostly on food processing and generally rely on others to conduct

basic research on new crops and new products.

Adequate funding is lacking for R&Din plant

screening for chemicals and for development

of new crops bearing such chemicals. Competition for current funds is keen. Unstudied plants

have no markets or products when they are

first investigated, and even with research it is

not certain that the plant will yield useful products. Should new products be developed, markets for them may not exist, or if they do exist

the market demands already may be being met

by other materials from different sources. The

history of agriculture shows that the major U.S.

crops have depended heavily on large Government expenditures for research, development,

and farm subsidies. The development of a new

crop in the past has not and probably cannot

now depend solely on the efforts and funding

of the private sector. Bringing new crops into

the marketplace usually requires a long period of time. During this time of R&D the commitment for continuity of support is key to

maintaining industry’s interest. The private

sector is unlikely to be willing to pay all costs

for developing a plant product or risk working on the crop at all unless assured that a continuing commitment to the crop’s research and

development exists. It seems likely that Federal

support in the form of Government research

and funding for private research will be required to move crop or product development

along to a point where the private sector ultimately can take over.

In addition to its role in carrying out or funding research, the public sector has a role in providing incentives or minimizing disincentives

in order to stimulate private sector interest in

commercial development of plant chemicals.

Such incentives might include tax benefits or

other forms of subsidies for farmers and industries developing new crops and plant products.

Disincentives to industry’s participation in this

area include uncertainties in patent laws. Some

industries seem to feel that existing product or

processing patents offer insufficient protection

against competitors. There also seems to be

some confusion about the patentability of plant

material. Although university-industry cooperation represents an advantageous meshing of

expertise and funding, industry often hesitates

to enter into such arrangements for fear of insufficient control over research results. For the

same reason industry may hesitate to engage

in research protected under a publicly owned

patent, protection of key research findings cannot be assured. OTA workshop participants expressed a concern over perceived problems

arising from patent law. They see a need for
60 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

the Government to examine certain patent laws

as they apply to plant-extract industries and,

where appropriate, change these laws to provide adequate incentives to industry to invest

in plant-chemicals research.

Clearly, if the potential for commercial development of plant chemicals is to be exploited,

R&D in this field needs to be coordinated

among Government, academia, and industry. *

In light of increased concern over rapid loss

of genetic plant material worldwide, increased

action in this area seems appropriate now. The

role of Congress could include the following

actions:

1. Congress could request an evaluation of

the status of science and technology related to extracting chemicals from plants

and the development of associated new

crops. The study would assess at least the

following three issues:

●

●

●

basis for a coordinated plan for commercial production of plant extracts and

developing associated new crops;

funding requirements for long-term

R&D;

incentives and patent-law uncertainties

that might be a disincentive for industry

involvement.

The study could examine and assess the

major constraints to and opportunities for

*One attempt at coordinating research and development on

new crops is contained in Public Law 95-592, Native Latex Commercialization and Economic Development Act of 1978. In the

act, a Federal agency coordinating commission was established

to oversee R&D work on Guayule. In 1983, the commission membership and scope were broadened under H.R. 2733, Critical

Agricultural Materials Act. As of this writing, the bill has passed

the House and full Senate action is pending.

2.

3.

establishing new industries that could extract important chemicals, medicines, and

protein, for example, and develop associated new crops. It could assess ways to

minimize the constraints and to analyze

potential impacts of taking such actions.

The study could outline possible ways

to establish a mechanism for Congress to

obtain continuing information and advice

on plant-chemical industries and associated new crops, research priorities, and

methods for improving coordination

among Government, industry, and academia.

Congress could hold a series of hearings

to address such issues as:

●

●

●

●

the need for a coordinated plan for

R&D of plant extracts and associated

new-crop development;

the needs for R&D funding;

incentives and patent-law uncertainties

that might be a disincentive for industry involvement; and

consideration for the establishment of

a “plant extracts/new crops advisory

council” comprised of members of Government, academia, and industry.

Participating committees could be those

having jurisdiction over such topics as

agriculture, science and technology, commerce, marine environment, international

development, medicine, strategic stockpiles, and public health.

Upon completion of such hearings, Congress could, if the need is justified, take

appropriate actions to form a permanent

“plant extracts/new crops advisory council. ”
Appendix

Technical Papers
AN ALTERNATE USE FOR TOBACCO AGRICULTURE:

PROTEINS FOR FOOD PLUS A SAFER SMOKING MATERIAL

Samuel Wildman

Santa Monica, Calif. *

Tobacco could be developed as an important food

crop in combination with its traditional use for

smoking and chewing. As a food crop, tobacco

grown in dense spacing could produce about four

times more protein per acre than soybeans and

about five times more dry tobacco for smoking than

conventional tobacco crops. A simple method has

been developed for extracting the proteins from the

aerial portions of fresh tobacco and other plants.

The water soluble proteins have unique nutritional

and functional properties that could make them

valuable for the package food industry and for

medical use. The insoluble proteins have properties similar to soy protein. A byproduct of growing tobacco for food proteins is a deproteinized

smoking tobacco that has lower concentrations of

chemical compounds known or suspected to have

adverse effects on cigarette smokers,

Plant, Extraction Products,

and Extraction Techniques

Ninety-nine percent of the tobacco used for smoking and chewing is obtained from Nicotiana

tabacum. This plant was a weed believed to have

been domesticated in Latin America long before

Columbus’ discovery of the New World. Today tobacco is grown on every continent except Antarctica, and is found in both hemispheres at latitudes

from the Equator to 55°. World demand for tobacco is enormous and, despite smoking’s adverse effects on health, the demand continues to grow. At

least 4 trillion cigarettes were consumed in 1981.

About 2.5 million hectares (6,2 million acres) of

land worldwide are devoted to tobacco plants that

are used exclusively for smoking and chewing.

China uses nearly a million hectares for growing

tobacco, and the United States nearly 400,000 hectares, followed by smaller areas in nearly every

other country in the world.

Some people believe that the future of tobacco is

in jeopardy, at least in Western countries where per

capita tobacco consumption is declining. Tobacco

is being attacked increasingly by health authorities,

● Retired, Leaf Protein International, Inc.

as medical evidence accumulates on the adverse effects of smoking on health. However, this situation

could change because a simple process that extracts

high-grade proteins suitable for human consumption from tobacco plants has been developed (9). A

byproduct of the extraction process is a deproteinized cigarette tobacco (10) considerably reduced

in components hazardous to smokers’ health,

Potential Uses of Major

Extraction Products

The extraction process perfected to a pilot plant

stage by Leaf Proteins, Inc. (LPI) yields the following six potentially useful products.

1. Crystalline Fraction 1 protein. This product

constitutes more than 30 percent of the total protein in tobacco leaves. It is soluble in water, is

tasteless and odorless, and is composed entirely of

amino acids of high nutritional quality. When fed

to rats, crystalline Fraction 1 protein exhibited a

somewhat higher protein efficiency ratio (PER)

than casein, the standard commonly used for comparing the nutritional quality of proteins (4).

Crystalline Fraction 1 protein has unique properties that might be used in medicine. When washed

free of sodium and potassium, the crystals might

be used in patients with kidney failure to meet their

amino acid requirement without taxing the kidney’s

inability to eliminate cations. Crystalline Fraction

1 might also be used to meet the entire protein requirement of patients with acute gastrointestinal

problems or patients recovering from surgery of the

alimentary canal. The amino acid mixtures used in

patients with kidney disease are expensive and they

taste, at best, vile. Since crystalline Fraction 1 protein is tasteless, it could be incorporated into appetizing diets and is potentially more economical

than amino acid mixtures now used.

Properties of crystalline Fraction 1 protein render

it potentially useful to the package food industry.

Because it is tasteless and odorless, it could be

added to food without altering the food’s taste and

smell. As a dry, almost white powder, it could be

mixed with cereal grains to improve their protein

content and quality. It might be used as a milk

substitute in countries that lack a dairy industry.

In its soluble form, it could be added to soft drinks,

removing them from the junk food category. Similar to egg albumin, Fraction 1 protein irreversibly

gels when heated above 80° C (176° F). Its func63
64 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

tional properties, such as “heat set,” are similar to

egg albumin or casein that are widely used throughout the package food industry. The amino acid composition, protein efficiency ratio (PER) data, and

data concerning functionality properties of Fraction 1 protein are given in appendix 1.

2. Fraction 2 protein. This product also is watersoluble and of high nutritional value. Its main use

could be as a supplement to upgrade the nutritional

quality of cereals and other food products. The

functional properties of Fraction 2 protein are less

desirable than those of Fraction 1 protein, but improvements in extraction procedures may eliminate

this difference. The amino acid composition of

Fraction 2 protein is shown in appendix 2.

3. Green sludge. This product consists mainly of

water insoluble proteins and starch. Because it also

contains beta carotene and xanthophyll, green

sludge could be marketed as a supplemental feed

for poultry and monogastric animals. By solvent extraction, green sludge can be converted into a material similar in properties and amino acid composition to defatted soybean meal. The decolonized material could be used in the food industry for the

same purposes as soybean meal. The essential amino acid compositions of green sludge protein and

of soy flour protein are compared in appendix 3.

4. Green residue. This product is a fibrous

material whose solids are composed of more than

50 percent cellulose and hemicellulose and about

13 percent protein. Its nutritional value is similar

to that of alfalfa hay. By solvent extraction, green

residue is dehydrated and converted into white

fibers that can be used for manufacturing deproteinized cigarette tobacco. The chemical composition of dried green residue and a comparison of the

composition of white fibers and wheat bran are

given in appendix 4.

5. Pigments and other bio-organic compounds.

These are products of organic solvent extraction of

green residue and green sludge. The material can

be separated further into chlorophyll, carotenes and

carotenoids, solanesol, and other compounds of lipoidal nature. Poultry producers use large quantities

of purified carotenoids.

6. Low molecular weight compounds. This product is composed of water soluble sugars, amino

acids, vitamins, salts, and other compounds. When

concentrated by evaporation of water to about 10

percent solids, the product probably could be used

as a fermentation liquor. The product is used as a

flavoring and coloring material which, when added

to the white fibers, produces a deproteinized cigarette tobacco low in components thought to be

harmful to health. The apparent tar and nicotine

composition of LPI deproteinized tobacco and conventional cigarette tobacco are compared in appendix 5.

Processing Technique

Operation of a pilot plant in North Carolina during 1981 and 1982 demonstrated the commercial

feasibility of the LPI process for obtaining

crystalline Fraction 1 protein and the other raw

materials from tobacco. The processing technique

is diagramed in figure 1. There are six steps of

the LPI process as described below,

1, Disintegration of plants. The aerial portions

of fresh tobacco plants are placed on a conveyor

(fig, 2) for transport to the mouth of a Rietz DisinFigure 1 .—Schematic of the LPI Process for

Obtaining Proteins and Other Products

From Tobacco and Other Plants

Process for producing tobacco proteins

Green

residue

Brown

juice

Plants Green sludge Fraction 2 proteins

Crystalline

Fraction 1 protein

Figure 2.–Conveyor Transporting About 15 lb

of Tobacco Plants per Minute at Beginning

of LPI Process
An Alternate Use for Tobacco Agriculture: Proteins for Food Plus a Safer Smoking Material • 65

tegrator (fig. 3), where the plants are sprayed with

a 0.5 percent solution of sodium metabisulfite in

water as they fall into the pulping device. Sodium

metabisulfite, listed as GRAS, is used widely in the

food industry. It is the only exogenous chemical

added during the extraction process.

Z. Extraction of green juice from disintegrated

plants. The pulp emerging from the disintegrator

is pumped into a Rietz Rotary Press (fig. 4) where

pressure from a mechanical screw forces out a

green juice through a fine-mesh screen while retaining the green residue until it is discharged into a

wheelbarrow (fig, 5) at the other end of the press.

3. Removal of green sludge from green juice.

The green juice emerging from the press is pumped

through a heat exchanger so that the juice is heated

rapidly to about 1250 F, then cooled rapidly to room

temperature. The abrupt temperature change aids

Figure 3.—Plants Falling Off Conveyor Into Mouth of

a Rietz Disintegrator

White pipe at 60° angle at top right is fitted with a nozzle to spray

plants with 0.5 percent sodium metabisulfite solution as they

pass into pulping chamber. Pulp is pumped (lower right) to the

press shown in figure 4

Figure 4.—Hose Containing Pulp Being Conveyed

to Opening of a Rietz Rotary Press

Green juice is squeezed out through fine-mesh, stainless steel

screen in center of press and drips into sump beneath. Green

residue is forced by rotating screw to left end of press

for discharge

Figure 5. —Wheelbarrow Located Beneath Press To

Catch Discharged Green Residue With Moisture

Content of About 65 Percent

in particulate matter aggregation to which the

green pigments and other lipoidal compounds are

attached. The juice then enters a Westphalia SB-7

Continuous Flow Centrifuge (fig. 6) which removes

all of the starch and about 85 percent of the green

particulate material which is discharged periodically as green sludge (fig. 7). A partially clarified

brown juice emerges from the centrifuge.

4. Filtration of brown juice. The partially

clarified brown juice containing soluble proteins

is pumped to a Rotary Vacuum Filter (fig. 8) whose

filter is made out of diatomaceous earth. The filter

removes the last traces of green sludge. The clear

brown juice (fig. 9) emerging from the filter (fig. 10)

is sent to a storage tank where crystallization of
66 . p/ants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Figure 6.—Westphalia Disk Type Centrifuge Figure 8.- Rotary Vacuum Filter Whose Surface is

Covered by a Thick Layer of Diatomaceous Earth

Which Dips Into a Reservoir of Plant Juice

(obscured In photo) as it Rotates

Used to remove about 65 percent of green sludge from green juice

coming from press and after having been heated momentarily to

150° F and cooled to ambient temperature on the way. Green juice

enters centrifuge at top and exits via plastic hose partially hidden

by dial (center of photo) on way to rotary press shown in figure 7

Green sludge not previously removed by centrifuge In figure 6

is caught on surface of filter while brown juice containing soluble

proteins is sucked through the pores of the filter cake by the

vacuum. Green sludge “blinds” the filter so that the surface must

be constantly renewed by the knife seen removing very thin layer

of filter cake so that a renewed filter surface reenters the reservoir

of plant juice at bottom of filter

Fraction 1 protein begins within 3 to 6 hours of storage and is completed within 3 to 4 hours after the

first crystals appear. If left undisturbed, the crystals

will settle into a layer at the bottom of the vessel.

5. Collecting and washing Fraction 1 protein

crystals. Because funding limitations have precluded purchase of equipment for a more efficient

washing method, the crystals are collected by passage through the SB-7 centrifuge and the mother

liquor is sent to a storage tank. The crystals are

resuspended in tap water followed by recentrifugation and a second washing cycle. After the crystals

are discharged from the centrifuge and allowed to

settle, they compact into a nearly colorless suspension of about 10 percent protein in water (fig. 11).

6. Collecting and washing Fraction 2 protein.

While not a desirable method because of denaturation of proteins, limited resources necessitated adding acid to the mother liquor to precipitate the Fraction 2 proteins at pH 4. The Fraction 2 protein precipitate is collected by centrifugation, and the

brown liquid containing the low molecular weight

compounds is sent to a storage tank. The precipitate

then is resuspended in water and washed in the

same manner as the Fraction 1 protein crystals.
An Alternate Use for Tobacco Agriculture: Proteins for Food Plus a Safer Smoking Material ● 6 7

Figure 9.— Brown Juice Coming From Rotary Vacuum

Filter at About 4 L/rein (1 gal/min) Entering

Storage Tank Where Crystallization of

Fraction 1 Protein Will Occur

Figure 10.—Appearance of Brown Juice Before

Crystallization of Fraction 1 Protein Has Occurred

Showing It – - - To Be Devoid “ of Green Sludge

Level of Development of Technology

LPI, a California corporation, developed and patented its simple method for obtaining crystalline

Fraction 1 protein and developed and patented a

method for converting green residue into a deproteinized tobacco suitable for cigarettes, To explore

the commercial possibilities of the protein extraction process, LPI formed a joint venture with the

North Carolina Farm Bureau Federation which, together with General Foods Corp., provided funds

and equipment to construct a pilot plant at Lucama,

N. C., in the heart of the flue-cured tobacco region.

The pilot plant was operated for the first time in

August 1980, but was unable to produce Fraction

1 protein of desired purity during the remaining

2 months of the growing season. The following

summer, acceptable Fraction 1 protein was made

in a few experiments, but unusual drought conditions destroyed much of the plant material designated for the pilot plant program. Each experiment

required a minimum of 600 lbs (272 kg) of fresh

plants. Not until July 1982 could the pilot plant consistently produce crystalline Fraction 1 protein of

high purity. As of September 1982, the pilot plant

has operated without failure on 14 occasions to produce Fraction 1 protein crystals. The plants used

in these experiments were harvested from various

fields, at various stages of growth, and after exposure to various climatic conditions. The success

of the pilot plant operations conducted during 1982

demonstrates the feasibility of the LPI process as

a method of producing pure Fraction 1 protein and

its byproducts on a commercial scale.

The existing pilot plant is capable of processing

about 1 gallon (3.785 l) of plant juice per minute or

about 1 ton of fresh tobacco plants during a 6-hour

run. After 6 hours, the process flow must be interrupted for 3 to 4 hours to clean up and remake the
68 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Figure 11.—Appearance of a Suspension of Washed

Fraction 1 Protein Crystals

Crystals obtained by processing about 1 ton of tobacco” plants

by the LPI process. Crystals have settled below the 60 L mark

on the vessel, the layer of crystals consisting of about 10 percent

Fraction 1 protein (dry basis)

filter cake. With another rotary filter, the pilot plant

could be operated continuously. With larger capacity filters, the process rate could be doubled or

tripled without changing the other equipment. With

a larger capacity disintegrator, the process could

handle 5 gallons (19 l) of juice per minute.

According to laboratory determination, the yield

of raw products from 1,000 kg of fresh tobacco

plants is as follows:

● 20 kg of Fraction 1 protein crystals (80 percent

water);

● 10 kg of Fraction 2 protein precipitate (80 percent water);

● 250 kg green residue (64 percent water) containing raw material for cigarette tobacco;

● 100 kg ton green sludge (70 percent water) containing insoluble proteins and starch; and

● 1,060 1 (280 gal) of brown liquid containing 2

percent low molecular weight, water soluble,

solids.

Wet Fraction 1 protein crystals were shipped to

a custom, spray-drying company which found that

spray-drying produced a powder of Fraction 1 protein that was stable at room temperature. The powder readily dissolved in water to produce a Fraction 1 protein solution with properties equivalent

to those before drying.

Table 1 shows the expected yield of dry Fraction

1 protein and its finished byproducts per 60 tons

of fresh tobacco. This is the average biomass of

closely grown tobacco plants expected per acre per

growing season in a climate like that of North Carolina. The figures in column 3 of table 1 are based

on existing pilot plant yields, but for realization

would require additional spray-drying capacity of

1.3 gal/hr (4.9 l/hr), water evaporation capacity of

Table 1.—Yield and Estimated Value of Finished Products From Tobacco

At 60 ton plant/acre/

Minimum estimate growing season

of wholesale

Finished product value Yield (dry) Value

White fibers for cigarette tobacco . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30¢/lb 5.3 ton $3,500

Decolonized insoluble protein + starch (equivalent to soybean meal) $150/ton 1.8 ton 290

Carotenoids for poultry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $7/02 (25¢/gram) 13.2 lb (6 kg) 1,500

Fraction 1 protein (equivalent to egg white) . . . . . . . . . . . . . . . . . . . . $1.81/lb ($4/kg) 529 lb (240 kg) 980

Fraction 2 protein (equivalent to soy protein) . . . . . . . . . . . . . . . . . . . 45¢/lb ($ I/kg) 265 lb (120 kg) 120

Condensed brown liquid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . No estimate 1.4 ton No estimate

$6,370/acre
An Alternate Use for Tobacco Agriculture: Proteins for Food Plus a Safer Smoking Material ● 6 9

13 gal/hr, and organic solvent extraction and recovery capacity of 5.3 gal/rein. Column 4 shows the estimated dollar value of the products based on the

minimum estimate of wholesale value in column 2.

State of Art; Additional

Research and Development

As mentioned earlier, the SB-7 centrifuge was

used for collecting and washing Fraction 1 protein

crystals. Preliminary studies indicate that washing

Fraction 1 protein crystals by ultrafiltration or

reverse osmosis could be more efficient. Additional

comparative experiments need to be made before

deciding on which equipment to install for continuous operation.

Preliminary experiments on a laboratory scale

suggest the possible advantage of simultaneous concentration and washing of Fraction 2 protein by

ultrafiltration, a procedure that would avoid the

denaturation now caused by acid precipitation.

Further experiments are needed before deciding on

the best equipment to install for continuous production of the Fraction 2 protein product.

More work needs to be done on solvent extraction of green residue and green sludge and on methods for recovering the solvent and refining the carotenoids and other compounds extracted by the organic solvent. Preliminary work need not be on a

scale to keep up with the green juice process

stream, but should be at a level sufficient to produce 5 to 10 lb batches of white fibers needed for

evaluation by tobacco manufacturers.

Other Sources of the Extracttion Product

About 40 years ago, N. W. Pirie (8) of England

advanced the idea of using leaf proteins for human

food and developed a technology for extracting

them from various plant species, While nutritious,

the protein preparations were green colored and

had an odor, taste, and texture that made them

largely unacceptable to the human palate,

1. Pro-Xan process for obtaining alfalfa proteins. A group at the USDA Western Regional Research Laboratory under the leadership of Dr. G.

O. Kohler modified and enlarged the Pirie process

to where 10 tons/day of alfalfa leaf protein known

as “Pro-Xan” could be produced for animal feed

(5), A plant of this capacity consumed 40 tons/hr

of green chopped alfalfa. In 1977, the cost of such

a plant was estimated by USDA to be $3,334,477

(3). The annual operating cost, for 22 hr/day and

130 days/yr, was estimated to be $401,796, Field

chopped alfalfa is treated with ammonia while being crushed to express a green plant juice whose

proteins then are coagulated by heat. When dried,

the green Pro-Xan contains 57 percent protein, 9

percent lipoidal material, and 100 mg xanthophyll

per kg. Xanthophyll, a yellow pigment, is valuable

for the color it imparts to chicken flesh and egg

yolks. Industrial plants were in operation until the

market for dehydrated alfalfa disappeared in the

United States. A Pro-Xan II process evolved to the

pilot plant stage whereby a Pro-Xan type of product containing less protein and more lipid was

removed before the remaining soluble proteins

were coagulated by heat to produce, when dry, a

bland, off-white material containing 90 percent protein (2). The off-white protein was greatly improved

in the organoleptic properties that prevented acceptance of the original Pro-Xan by humans. Table

2 shows some of the differences in quality of the

products produced by the Pro-Xan II process from

alfalfa compared with the products produced by the

LPI process from tobacco.

2. LPI process for alfalfa and other plants. The

products enumerated in table 1 have also been obtained on a laboratory scale by the LPI process from

the aerial portions of alfalfa, soybean, clover, and

Table 2.—Quality of Products Obtained From Alfalfa Plants by the Pro-Xan II Process

Compared With Those From Tobacco Plants by the LPI Process

Product Alfalfa Tobacco

Green residue . . . . . . . Can be used only for animal feed Used for deproteinized cigarette tobacco and

for animal feed

Green sludge. . . . . . . . Same as tobacco Same as alfalfa

Fraction 1 protein. . . . Denatured together with Fraction 2 protein to Obtained as crystals containing more than

yield water insoluble material containing 90°/0 99°/0 protein which redissolves in water

protein

2% of total solids 4% of total solids

No functionality Functional properties similar to egg white

Some taste and color Odorless and tasteless

Fraction 2 protein. . . . Denatured and mixed with Fraction 1 protein Contains no Fraction 1 protein

2°/0 of total solids
70 . Plants: The potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

sugar beets, and probably could be obtained from

other plants with succulent leaves such as cotton,

tomato, eggplant, spinach, etc.

3. USDA method for obtaining tobacco proteins

as byproducts of the homogenized leaf curing

process, USDA has been developing a process

known as homogenized leaf curing (HLC) that was

conceived by Dr. T. C. T’so and associates as a

means to provide a simplified industrial method for

producing safer tobacco. Donald De Jong and Jesse

Lam, Jr. (1) set up a pilot plant at Oxford, N. C., for

recovering edible proteins from the plant juice released during the pulping process at the beginning

of the HLC process. After squeezing the green juice

from the residue, green sludge is removed from the

juice by centrifugation. The soluble proteins then

are precipitated by acid and the deproteinized liquid is added back to the green juice. The mixture

is allowed to incubate at ambient temperature before being dried and made into deproteinized, reconstituted tobacco sheet for cigarette manufacture. The acid coagulated proteins are less valuable

than crystalline Fraction 1 protein from tobacco

because acid denaturation destroys the functional

properties of the protein. However, it would be relatively simple to modify the Oxford pilot plant to

produce crystalline Fraction 1 protein by the LPI

process.

Use of Technology

LPI was founded in 1979 with the goal of transforming tobacco into a commodity used on a large

scale for human food as well as for smoking. Private

capital supported the pilot plant operation. A great

opportunity exists for the private sector to participate in developing the pilot plant process into a

profitable commercial venture. The possible role

for government is twofold. First, it could have a

short-term role in providing financial aid to perfect

the process so that large enough quantities of the

products can be made for long-term animal feeding

tests. These tests are needed to obtain FDA approval before Fraction 1, Fraction 2, and the insoluble

proteins can be marketed for human consumption.

Second, government could support testing of the

health effects of deproteinized tobacco relative to

conventional tobacco. If deproteinized tobacco prepared by the LPI process is less hazardous, governmental involvement with this product is justified

by national health considerations.

Agronomic Considerations

and Requirements

Agricultural Scales and Systems

1. Biomass in relation to protein yield. The

agronomic factors that affect smoking quality and

now determine the value of conventional tobacco

are not so important when tobacco plants are to be

used for proteins and deproteinized tobacco. During processing of the green residue into reconstituted cigarette tobacco, flavorants can be added to

make the product acceptable to smokers, Thus, the

most important agronomic factor affecting commercial development of the LPI process will be

maximizing production of plant biomass per unit

of land per growing season at minimum cost.

Production of biomass is a direct function of

photosynthesis. The amount of photosynthesis is

related to the total area of green leaves exposed to

the sun (7). When the bottom leaves are shaded

from sun and turn yellow, the photosynthate accumulated in the form of starch, proteins, sugars,

and other compounds is destroyed in a secondary

process of supplying nutrients to the roots and topmost portion of the plant where rapid growth is occurring. A balance is reached where further growth

in the biomass will not increase the protein yield

per unit of biomass. This balance exists when the

canopy of plant leaves completely covers the

ground and the plants have grown until the leaves

nearest the ground start to turn yellow. At this

point, the plants should be harvested and processed

for maximum yield of proteins.

2. Multiple harvests of densely spaced plants.

Tobacco has tiny seeds, so plantlets arising from

seeds also are small and vulnerable at the beginning

of the growth period. With ideal conditions of moisture, soil fertility, temperature, duration of sunshine, and freedom from insect and parasite attack,

in 5 to 6 weeks the seedling could grow to a height

of 18 to 20 inches with its leaves covering an area

of 1 square foot or more. Under these conditions,

a planting density of 44,000 plants per acre would

produce a closed canopy 5 to 6 weeks after seeding.

Periods of drought, inclement weather, etc. would

lengthen the time until the canopy is closed. One

or two weeks of additional growth after the canopy

closes brings the biomass to the balance point at

which it should be harvested.
An Alternate Use for Tobacco Agriculture: Proteins for Food Plus a Safer Smoking Material ● 7 1

During harvest when the stalks of tobacco plants

are cut off about 4 inches above the ground, each

stalk will regenerate two to three new aerial shoots.

If soil fertility and moisture are maintained, the

new shoots will grow rapidly and form new leaves,

soon growing to a size close to that of the previously

harvested shoot. The leaf canopy of closely spaced

plants with regenerated shoots will close in about

5 weeks, so that a second harvest of biomass can

be made about 6 weeks after the first harvest. By

this process of “rattooning,” four biomass harvests

have been obtained from the same plants in the

5-month growing season in North Carolina. The appearance of densely grown plants ready for a first

harvest in early June 1982 is shown in figure 12.

3. Dense spacing by transplanting. Because of

their small size, tobacco seeds are usually germinated in plastic-covered seed beds whose soil has

been fumigated with methyl bromide to eliminate

diseases and, most importantly, to prevent weeds

from germinating and crowding out the smaller tobacco plants. The tobacco seeds are sown at a density of about 100 seeds per square foot, and about

2 months after germination are ready for transplanting. With existing farm equipment, transplants

for protein production could be spaced at about

30,000 plants per acre so that closing the canopy

might require 7 to 8 weeks with a similar time interval between rattoon harvests.

4. Close-spacing by direct sowing of seeds. It is

likely that the need for transplanting can be avoided

in growing tobacco for protein production. For example, each year S. P. Willingham of Florida grows

160 acres of directly seeded, closely spaced tobacco seedlings, which he sells for transplants to other

tobacco farmers. To avoid fumigation he clears new

Figure 12.—Close-Grown Tobacco Plants in North

Carolina Ready for a First Harvest for Protein

and Deproteinized Tobacco in June 1982

palmetto scrubland each year and prepares the soil

in 6-foot-wide beds raised 6 to 8 inches above the

surrounding soil. The region is frost-free and irrigation keeps the small plantlets moist during their vulnerable period immediately after germination.

There is no need to cover the beds with plastic.

Even when sown in the cool period during the last

week of December, in 60 days the plants will have

grown to harvestable size for protein production.

The disadvantage of the system is the requirement

for new land each year.

Chemical growth retardants that kill grass-like

plants without harming tobacco are available. Experiments in Florida and North Carolina indicate

that directly sown tobacco seeds could be grown

in dense spacing on a raised bed system such as

Willingham’s. Weed control would be accomplished by proper cultivation of the soil prior to

sowing and by use of selective growth retardants

after germination of tobacco seeds. As in Florida,

success of the system would depend on a reliable

irrigation system.

Tobacco seed can be pelleted, making it possible

to sow the seed in rows. Curtis Griffin of Florida

has developed machinery that could be modified

to sow seed in dense spacing within a row.

5. Cultivars of tobacco. Conventional tobacco

agriculture uses the species Nicotiana tabacum

almost exclusively. Different cultivars of N.

tabacum are used to obtain desirable flavor or other

qualities. Examples are the NC 95 cultivar grown

extensively in the flue-cured region of North

Carolina and the KY 14 cultivar grown in the burley

producing States. Cultivars not in use now may

prove more desirable for protein and deproteinized

tobacco production. Some cultivars produce less

than 10 percent of the nicotine ordinarily found in

tobacco. Other cultivars do not produce flowers until late in the growing season, which could increase

the biomass yield. Professor R. C. Long, of the

Crops Research Department of North Carolina

State University, has compared biomass yield of different cultivars commonly used for conventional

tobacco agriculture but grown at dense spacing. In

1981, the annual biomass yield ranged from 59 tons/

acre for a TI 174 cultivar to 38 tons/acre for a V

174 cultivar. The V 174 cultivar also had a 30 percent less protein yield than TI 174. Selection of the

proper cultivar for a particular geographical region

evidently will be an important factor in attaining

maximum yield of biomass.

To keep ahead of disease problems, new cultivars

of tobacco are constantly being developed by plant

breeders. In North Carolina, a new cultivar is released from experiment stations to growers about
72 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

every 5 years, Genes for resistance to diseases

found in some cultivars, or even in different species

of Nicotiana, are transferred by hybridization to

cultivars with desirable traits for smoking tobacco. The process of transferring a desirable gene may

require several successive hybridizations to eliminate undesirable genes accompanying genes for

disease resistance. Some intermediate hybrid

cultivars of no use in conventional tobacco agriculture could have characteristics valuable for protein

production, such as hybrid vigor and disease resistance.

Inputs Required for

Implementation of Technology

Professor Long proposed a system for growing

closely spaced tobacco for protein production using

conventional nursery practices. A l-acre nursery

would yield enough plants to transplant 9 acres at

a density of 84,000 plants per acre while leaving

a similar density of plants in the nursery. The biomass from the 10 acres would be harvested four

times. Long (6) estimated the following inputs:

1. Preparation of nursery seed bed. Materials:

Seed, 6.8 oz/acre; fertilizer, 3,400 lb/acre; fungicide

and insecticide, 90 lb/acre; herbicide, 13 lb/acre;

fumigation, plastic cover, and irrigation ($1,960/

acre). Labor: fumigation, plowing, fertilizing, sowing seed, etc. (82 hr/acre at minimum wage).

Machinery and Overhead: tractor, truck, spraying,

rolling plastic cover, irrigation (32 hours at average

cost of $14.20/hr).

2. Preparation of land for transplants. Materials: fertilizer, 1,681 lb/acre ($151/acre); nematicide,

herbicide, insecticide ($86/acre). Labor: lan d

preparation, spraying, fertilizing (3 hr/acre); transplanting (143 hr/acre at minimum wage). Machinery and Overhead: tractor, truck, sprayer, irrigation (36.3 hrs at average cost of $23/hr).

3. Four harvests of biomass and inputs for three

periods of regrowth. Materials: fertilizer (3,200

lb/acre or $213/acre); herbicide, insecticide ($20/

acre). Labor: harvesting, hauling, spraying, irrigating (11.7 hr/acre at minimum wage). Machinery

and Overhead: harvester, tractor, truck, sprayer,

irrigation (10.9 hr/acre at average cost of $23/hr).

Adding land rent at $75/acre, irrigation at $120/

acre, interest on investment (at 20 percent for 6

months) at $160/acre, and profit at $200/acre, total

input cost for the North Carolina transplant system

was estimated to be $2,275/acre.

With a direct seeding system of the type used in

Florida, input cost was estimated to be $1,900/acre;

because of the longer growing season this figure

includes five harvests with an annual yield of 75

tons of biomass/acre.

Scientific, Environmental r Economic,

Cultural, and Political Aspects of

DeveIopment and Implementation

of Technology

Engineering. As stated earlier, there appear to

be no unsolved engineering problems to constrain

large-scale expansion of the LPI process. Plants

capable of processing 40 tons of biomass per hour

have already been used to extract the green juice

from alfalfa. For a yield of 60 tons/acre in North

Carolina, a 40 ton/hr plant could process the biomass grown on 2,432 acres. The problems remaining before designing such a plant are of a development nature. Additional information is needed to

make proper choices among the various types of

equipment available to minimize operating costs for

labor, power, water, maintenance, and overhead.

Environmental. In the LPI process, no aerial portions of the plants are discarded as waste except

the water which comprises 85 to 90 percent of the

biomass. The water is removed by evaporation of

the brown liquid residue and could be condensed

and used again, if economical. To be economically viable, solvent extraction of green residue and

green sludge would have to recover the solvent as

efficiently as factories engaged in hexane extraction of oil from soybeans. Solvents used in the LPI

process are less volatile and have higher flash

points than hexane.

Economic. The finished products (table 1) produced from tobacco biomass by the LPI process are

tobacco for smoking and food for human consumption. Private industry with manufacturing and marketing expertise in food products may be uncomfortable with the prospect of entering into the

manufacture and marketing of a smoking product

of equal or higher value than the food product. This

constraint could be overcome by organizing a company to construct and operate the factories that

make the finished products in table 1, all of which

could be stored at ambient temperature. The decolorized white fibers and condensed brown liquid

would be supplied to tobacco manufacturers for

further processing into smoking material. The proteins would be supplied to food processing manufacturers and pharmaceutical companies. The solvent-extracted pigments could be supplied as raw

stock to manufacturers that would refine and mar-
An Alternate Use for Tobacco Agriculture: Proteins for Food Plus a Safer Smoking Material • 73

ket the chlorophyll, beta carotene, carotenoids,

solanesol, and other compounds.

Consumer Acceptance. A significant barrier to

commercial exploitation of this technology is the

public’s image of tobacco as a poisonous plant.

Tobacco does indeed contain nicotine. However,

repeated analyses have been performed on crystalline Fraction 1 protein from tobacco grown to different stages at close spacing and after different rattoon harvests, Nicotine contamination was in the

parts per billion range, detectable only by the most

sophisticated methods of analysis. The contamination was far below the level of 2 parts per million

(ppm) that the Food and Drug Administration

(FDA) considers safe in poultry meat which gets

contaminated by nicotine-containing insecticides

used in poultry farms, The contamination of Fraction 1 protein is also far below the 2 to 3 ppm nicotine found naturally in tomatoes, eggplant, green

peppers, and tea.

Constant reminders of the link between smoking

and cancer and other debilitating diseases further

exacerbate the negative image of tobacco. Nicotine

is not oncogenic. Tobacco has to be burned to produce the oncogenic compounds found in smoke.

Smoke from burning leaves or charcoal-broiled

steaks also contains oncogenic compounds, but

they constitute no significant hazard to health

because of the infrequency of inhaling such smoke.

So it is not the nicotine nor the possible presence

of cancer-inducing chemicals in tobacco proteins

that constitute the problem with public acceptance.

The problem is tobacco’s negative image that is

constantly being reinforced by reminders of the

harmful effects of smoking, Thus, a food company

contemplating the market for products containing

tobacco proteins could be faced with an inability

to overcome the negative image of tobacco.

If those who see tobacco agriculture and cigarette

manufacture as a declining industry in the United

States are correct, the best interests of the tobacco

industry might be served by educating the public

on the virtues of tobacco as food and actively supporting efforts to produce less harmful tobacco for

smoking. However, the fact that the tobacco industry steadfastly refuses to accept as proven that

smoking is harmful to health makes their promotion of tobacco as food unlikely.

Government could play a decisive role in overcoming the problem of public resistance to the use

of tobacco for food. Existing government laboratories could perform the extensive testing of the

tobacco proteins required for FDA approval of their

use as a food additive. There is scientific evidence

indicating that tobacco proteins will receive a clean

bill of health after such testing. Then government

could exercise a publicity function to ensure widespread dissemination of unbiased data. In this function, the Office of the Surgeon General could be as

effective in changing the negative image of tobacco as it has been in educating the Nation on the

perils of smoking.

Cultural. As with other crops in the United

States, production of the conventional tobacco crop

has become increasingly more mechanized as new

types of farm equipment have become available. Intensive labor is required only for brief periods during transplanting, harvesting, and curing the crop.

The North Carolina transplant system to grow tobacco biomass for the LPI process would require

somewhat more labor for transplanting but less for

harvesting than the conventional system. Labor requirements would remain about the same so that

adoption of the new form of agriculture would have

little impact on existing cultural patterns. As direct

seeding of tobacco becomes perfected to replace

transplantation, tobacco grown for biomass would

become as mechanized and capital intensive as

corn, soybeans, alfalfa, and other crops.

Political. In the United States, conventional

tobacco is grown and marketed under a Government regulated allotment program that limits total

acreage in return for a basic support price for cured

tobacco. By leasing allotments, some farmers grow

100 or more acres of tobacco using mechanized

equipment as much as possible. Because efficient

farmers derive high income from tobacco, it is natural that the lessors and lessees of allotments will

zealously guard a program so favorable to their welfare. Since the individual allotment is usually less

than 3 acres, the number of individuals owning allotments is large, considering that almost 1 million

acres of tobacco are grown in the United States.

Their votes translate into a significant political

force.

Balanced against the political clout of the allotment holders are the public health concerns over

the hazards associated with the use of smoking

tobacco. These concerns have left their mark; this

year Congress required the allotment program to

operate without Government subsidies. The program has to be renewed annually by Congress, and

each successive renewal vote has become more

uncertain.

24 - 503 0 - 83 - 6
74 . P/ants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Impacts on Developed

and Developing Countries

Implementation of tobacco as a food crop in European countries would provide an alternate source

of protein and decrease the present need to import

soybeans that cannot be grown in many parts of

Europe. In Japan, which cannot grow enough soybeans to meet its domestic requirement, tobacco

would become an additional source of protein to

replace some soybean imports. Agriculture in developing countries in the Tropics is notable for lack

of crops of high protein content. Soybeans cannot

be grown in tropical climates, Tobacco, however,

is grown extensively in the Tropics and could

become a source of protein not previously available

because foreign exchange was not available to import soybeans. Tobacco protein could have tremendous impact by helping to alleviate malnutrition in

these countries.

High technology equipment is not required to use

tobacco for protein production, and analogs of the

equipment used by LPI in the United States are

readily available in all industrialized nations. Easy

availability of the equipment would help reduce the

cost of initiating production of the new food in developing countries. Less developed countries would

not have to import scientific know-how because the

LPI process is simple. Both domestic and foreign

patents of the process have been issued so that the

scientific information is available in the patent

literature. LPI views a logical development of the

technology as starting with a demonstration factory

in the United States which could train personnel

in the agricultural and processing aspects of tobacco for protein and the other finished products listed

in table 1.

When tobacco is grown for protein, the agricultural practice will conform to the existing cultural

and social patterns of the country in which it is

grown. In the United States, great emphasis will

be placed on mechanization. In countries with high

population density and land scarcity, cultivation of

tobacco for food may remain highly labor intensive.

Plants would be transplanted by hand at even closer

spacing than can be accomplished by transplanting

machines. Fertility, weed control, and harvesting

would be managed by people instead of costly herbicides, insecticides, and harvesting machinery,

and biomass production per unit of land could exceed that produced by a high degree of mechanization. Labor intensive cultivation of tobacco for protein could also have an impact by reducing the acreage used for smoking tobacco and making the land

available to grow other kinds of food crops. For example, China uses about 2.5 million acres for smoking tobacco. If only 30 percent of the LPI deproteinized tobacco were combined with 70 percent

conventional tobacco in Chinese cigarettes, about

400,000 acres now used for conventional tobacco

could be released because the yield of deproteinized tobacco per acre is about five times greater

than conventional tobacco. In addition, enough

crystalline Fraction 1 protein would be produced

as a byproduct of deproteinized tobacco to satisfy

the total annual protein requirement for 2.4 million

people, to say nothing of the Fraction 2 protein and

insoluble protein produced at the same time. At 100

percent deproteinized tobacco in cigarettes, 2 million acres could be taken out of smoking tobacco

and used for much needed food crops.

As in other parts of the world, the Chinese Government has become alarmed by the health hazards

caused by smoking tobacco. The health hazards associated with “tar” in burning tobacco have been

reduced in Western countries by filters and sophisticated techniques for diluting the smoke with air

before it enters the lungs, * but the materials required add appreciably to the cost of cigarettes,

Thus, another advantage that could accrue from deproteinized tobacco in developing countries is that

a significant reduction in tar producing ingredients

would have occurred during processing so that the

extra cost of filtration and dilution devices might

be

1.

2.

3.

4.

avoided.

References

De Jong, D. W., and Lam, J. J., Jr., “Protein Content

of Tobacco, ” Proc. of Amer. Chem. Soc. Symposium,

1977, pp. 78-103,

Edwards, R, H., et al., “Pilot Plant Production of Edible White Fraction Leaf Protein Concentrate From

Alfalfa,” ~. Agr. Food C%em. 23: 620-626, 1975.

Enochian, R. V., et al., “Producing Pro-Xan (Leaf Protein Concentrate) From Alfalfa: Economics of an

Emerging Technology,” USDA Agricultural) Economic Report No, 445, 1980.

Ershoff, B. H., et al., “Biological Evaluation of Crystalline Fraction 1 Protein From Tobacco,” Proc. S;c.

Expt, Biol. Med. 157: 626-630, 1978.

5. Knuckles, B. E,, et al., “Pro-Xan Process: Methods of

Increasing Protein Recovery From Alfalfa, ” J, Agr.

Food Chem. 20: 1055-1057, 1972.

*OTA footnote: Readers interested in characteristics of low-yield

cigarette use are referred to N. L. Benowitz, et al., “smokers of LOWYield Cigarettes Do Not Consume Less Nicotine, ” The New England Jour.

nal of Medicine, vol. 309, No, 3, July 21. 1983, pp. 139-142. The art ic]e

appeared in print while this proceeding was in press,
An Alternate Use for Tobacco Agriculture: Proteins for Food Plus a Safer Smoking Material ● 7 5

6,

7.

8.

9.

10.

Long, R. C., “Estimates of the Cost of Producing Tobacco for Protein, ” unpublished report made available to Leaf Protein International, Inc., Raleigh, N. C.,

January 1980.

Peterson, R. B., and Zelitch, I., “Relationship Between

Net CO, Assimilation and Dry Weight Accumulation

in Field-Grown Tobacco, ” P/ant Physio]. 70: 677-685,

1982.

Pirie, N. W., “The Direct Use of Leaf Protein in Human Nutrition,” Chern. & Jnd. 61: 4-48, 1942.

Wildman, S. G., and Kwanyuen, P., “Process for Isolation of Ribulose I-5 Diphosphate Carboxylase From

Plant Leaves,” U.S. Patent No. 4,268,632, 1981.

Wildman, S. G. and Sheen, S. J., “Process for Obtaining Deproteinized Tobacco Freed of Nicotine and

Green Pigment, for Use as a Smoking Product,” U.S.

Patent No. 4,289,147, 1981,

Appendix 1

Fraction 1 Protein

Also known as ribulose-1,5-bisphosphate carboxylase-oxygenase, the enzyme that catalyzes the

assimilation of carbon dioxide during photosynthesis, Crystals of Fraction 1 protein are insoluble in

water even though 80 percent water is an intrinsic

part of their structure. Crystals rapidly dissolve in

water containing traces of sodium, potassium, or

ammonium ions. When dried, the crystalline protein contains no nucleic acid, lipoids, or carbohydrates, and more than 99 percent of its composition is composed of amino acids with the composition shown below:

Amino Acid Composition of Fraction 1 Protein

g/loo

Amino acid g/protein AA g/100 g AA g/100 g

Ile . . . . . . . . . . . . . . . 4.3 Thr 5,2 Asp 8.5

Leu . . . . . . . . . . . . . . 8.8 Try 1.5 Ser 3.3

Lys ... , . . . . . . . . . . 5.8 Val 7,2 Glu 11.2

Phe . . . . . . . . . . . . . . 4.4 His 2.2 Pro 4.6

Tyr ., . . . . . . . . . . . . 4.9 Cys 3.0 Gly 9.2

Met. . . . . . . . . . , . . . 1.6 Arg 6.1 Ala 7.0

High nutritional value of Fraction 1 protein

shown by feeding rats with the PER results (4) summarized below:

Protein Efficiency Ratio (Weight Gained/Protein Consumed)

of Fraction 1 Protein Compared to Casein as Standard

Days after feeding

7 14 21 28

Casein . . . . . . . . . . . . . . . . . . . . . . . . 2.73 3.17 2.88 2.83

Fraction 1 protein . . . . . . . . . . . . . . 3.40 3.44 3.10 3.01

Exposed to trypsin, one of the digestive enzymes

of the human stomach, Fraction 1 protein rapidly

breaks down into about 80 tryptic peptides of small

molecular weight demonstrating its high degree of

digestibility. The native protein contains many sulfhydryl groups but no disulfide linkages.

Functionality studies were performed with three

different forms of crystalline Fraction 1 protein:

Crystals, washed free of salts by water, were spraydried before testing; pH 8.5, washed crystals were

redissolved with NaOH to pH 8.5 before spray-drying the redissolved protein; pH 3.0, washed crystals

were redissolved with NaOH to pH 10.5, then acidified to pH 3,0 with phosphoric acid before drying.

Foaming Capacity and stability

Foaming

capacity (ml) Foam stability (ml) after

Sample after 1⁄2 min 10 min 30 min 1hr 2 hr

Fraction 1 protein

(crystal). .. .....75 48 42 30 24

Fraction 1 protein

(pH 8.5) .. .....77 30 14 6 6

Fraction I protein

(@ 3.0) .. .....82 60 60 58 58

Soy protein* . . . . . 53 6 6 4 4

Eggwhite ., . . . . . . 62 18 14 14 10

● A product of Natural Sales Co , Pittsburgh, Pa , All Star, 95 percent protein containing lecithin and papain.

Water and Oil Absorption

Water (pH 5

acetate buffer) Crisco oil

Sample Percent weight increase

Fraction 1 protein

(crystal) . . . . . . . . . . . . . . . . . . . 180.7 105.8

Fraction 1 protein

(pH 8.5) . . . . . . . . . . . . . . , . . . . 319.0 304.5

Fraction 1 protein

(pH 3.0) . . . . . . . . . . . . . . . . . . . 393.3 375.5

Soy protein ... , ., . . . . . . . . . . . 272.1 187.5

Eggwhite . . . . . . . . . . . . . . . . . . . 466.9 144.4

Whipping property

Volume increase after whipping

Before add’n After add’n

Sample of sugar of sugar

Fraction 1 protein

(crystal) ., . . . . . . . . . , ., . . . . 6730/o 7800/o

Fraction 1 protein

(pH 8.5) . . . . . . . . . . . . . . . . . . 570 640

Fraction 1 protein

(pH 3.0) . . . . . . . . . . . . . . . . . . 633 670

Soy protein. . . . . . . . . . . . . . . . . none none

Eggwhite . . . . . . . . . ... , . . . . . 600 633
76 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Emulsifying Property

Protein concentration

Sample 1% 20A 4%

1. 40% oil

Fraction 1 protein

(crystal) . . . . . . . . . . . . . . . 18 cps 26 cps 45 cps

Fraction 1 protein

(pH 8.5). . . . . . . . . . . . , . . 30 33 117

Fraction 1 protein

(pH 3.0) . . . . . . ... , , . . . . 44 535 10379

Soy protein , ., ., , , . . . . . . 40 140

2. 40% oil + 1% each of NaCl and starch

Fraction 1 protein

(crystal) . . . . . . . . . . . . . . . 21 41

Fraction 1 protein

(pH 8.5) . . . . . . . . . . . . . . , 55 126

Fraction 1 protein

(pH 3.0). , . . . . . . . . . . . . . 26 30

Soy protein . . . . . , . . . . . . , 30 52

3. 20% oil

Fraction 1 protein

(crystal) . . . . . . . . . . . . . . . 8 8

Fraction 1 protein

(pH 8.5). . . . . . . . . . . . . . . 6 22

Fraction 1 protein

(pH 3.0) ., ... , . . . . . . . . . 43 281

Soy protein . . . . . . . . . . . . . 35 127

4. 20% oil + 1% each of NaCl and starch

Fraction 1 protein

(Crystal} ).....,.....,,.. 8 2 8

Fraction 1 protein

(pH 8.5), . . . . . . . . . . . . . . 28 55

Fraction 1 protein

(pH 3.0) . . . . . . . . . . . . . . . 4 9

Soy protein . . . . . . . . . . . . . 5 10

Appendix 2

Fraction 2 Proteins

Amino Acid Composition

978

166

343

112

151

12

45

539

442

28

133

11

29

6%

97 cps

284

too thick

18915

690

681

146

481

25

99

5941

696

55

159

139

55

Amino acid g/100 g protein AA g/100 g AA g/100 g

ASP . . . . . . . . 6.1 ALA 5.1 PHE 8.4

THR ... , . . . 4.6 VAL 10.5 LYS 3,9

SER . . . . . . . . 4.0 MET 4,1 HIS 5.0

PRO ., . . . . . . 8.2 ILE 3.8 ARG 10.4

GLU . . . . . . . . 8.9 LEU 4.1 CYS 0.8

GLY . . . . . . . . 3.5 TYR 8.8

Green

Essential

Appendix 3

Sludge

Amino Acid Composition of Green Sludge Protein

Compared With Soyflour Protein

g/100 g Protein

Tobacco insoluble

Amino acid Soyflour protein protein

THR . . . . . . , . . . . . . 3.6

MET . . . , ., . . . . . . . 1.0

ILE . . . . . . . . . ... , . 3.5

LEU . . . . . . . . . . . . . 6.4

TYR . . . . . . . . . . . . . 2.1

PHE , . . . . . . . . . . . . 4.7

LYS . . . . . . . . . . . . . . 5.1

Appendix

Green Residue

4.4

1.8

4.1

4.2

9.6

8.8

3.9

Chemical Composition of Dried Green Residue From Tobacco

(Average of Four Different Preparations)

mg/g mg/g % of ash

Protein .. .148 Ash . . . . . . . , . . . . . 53 K , .. .0.6 Ma , ..0.2

Starch. . . . 30 Cellulose , ... , .. .291 Ca. ., .0.6 S .. ...0,2

Lipids ... , 20 Hemicellulose . . ..413 Mg .. .0.15

Lignin ., . 45

Comparison in Composition Between Green Residue

Decolonized by Solvent Extraction and Wheat Bran

Percent total solids

Constituent White tobacco fibers Wheat bran

Cellulose . . . ., , . . . . . , 29 9

Hemicellulose . . . . . . . . 33 40

Lignin . . . . . . ... , . . . . 6 4

Starch . . . . . . . . . . . . . . 13 17

Protein . . . . . . . . . . . . . . 13 18

Oil . . . . . . . . . . . . . . . . . trace 4

Ash . . . . . . . . . . . . . . . . . 7 8
An Alternate Use for Tobacco Agriculture: Proteins for Food Plus a Safer Smoking Material . 77

Appendix 5

Low Molecular Weight Compounds

Protein, Nicotine, and Apparent Tar Content of LPI

Deproteinized Cigarette Tobacco Compared With

Two Kinds of Conventional Cigarette Tobacco

Percent dry weight

Product Protein N Nicotine Tar

Conventional flue-cured tobacco,

variety NC 95 . . . . , ., , . . . . . . . 2.25 2.0 6.77

Deproteinized NC 95 . . . . . . . . . . . . 1.84 0.6 0.70

Conventional burley tobacco,

variety KY 14 . . . . . . . . , . . . . . , 4.15 3.0 6.07

Deproteinized KY 14 . . . . . . . . . . . . 3.00 0.7 0.82
Leaf Protein Extraction From Tropical Plants

Lehel Telek

Science and Education,

Agricultural Research Service, Southern Region,

U.S. Department of Agriculture,

Tropical Agriculture Research Station,

Mayaguez, Puerto Rico

Protein and calorie malnutrition is widespread

in the less developed countries. Importing highgrade animal products, cereal grains, and animal

feeds puts a strain on these countries’ economies.

Leaf protein concentrates (LPCs) should be seriously considered as additional protein sources. Leaf

protein concentrates from alfalfa are prepared on

a large commercial scale in Europe and the United

States. Unfortunately, alfalfa has not been grown

successfully in the humid tropics, and a suitable

tropical replacement is needed for leaf protein extraction.

At least 500 introductions of tropical plants have

been tested at the U.S. Department of Agriculture’s

(USDA’s) Tropical Agriculture Research Station in

Puerto Rico. Potential plants for LPC production

have been evaluated and selected for further

research, Machinery has been developed which

may be suitable for laboratory, on-farm, village

level, and commercial extraction. Further research

is needed in agronomy and leaf protein extraction

and use. On-farm use is the most economical

system for the tropics, It is suggested that crude leaf

protein concentrate be used as human food only in

extreme emergencies.

Tropical Plants for Loaf

Protein Extraction

At the present growth rate, world population will

double in the next 30 to 40 years. This population

increase mainly will burden the lesser developed

countries in the humid lowland tropics, where the

current annual population growth rate is 2.3 percent and yearly increase in food production remains low. The demand for food of plant origin will

continue to increase, and the supply of meat will

decrease because yields of cereal grains in the

tropics generally are low and local production is

consumed by humans. This ever-widening food

shortage cannot be alleviated by conventional agriculture alone. As an additional source of protein,

leaf protein concentrates (LPCs) should be given

serious attention because leaves are abundant yearround in the tropics and many have high protein

content. With suitable plant material, the yield per

hectare per year of leaf proteins can be at least four

times higher than that of seed proteins.

Leaf protein concentrates for animal feed currently are manufactured from alfalfa in Europe, and

a new processing plant was started recently in the

United States. Because efforts to adapt alfalfa to the

tropics have been only marginally successful in a

few areas, possible tropical plant sources have been

investigated.

In 1978, a broad research program to find suitable

tropical plants for leaf protein fractionation was organized at the Tropical Agriculture Research Station, USDA (Science and Education) in Mayaguez,

Puerto Rico. At least 500 introductions were

planted and critically evaluated as potential sources

for LPC extraction (77) (table 1). The following criteria were used in selecting plants suitable for LPC

production: high protein and dry matter (DM) content, good protein extractability when freshly cut,

and good regrowth potential. The plants should fix

nitrogen, be erect and easily harvested mechanically, and be nontoxic and low in antinutritional

factors,

Freshly harvested plants were extracted in a

blender with 600 ml ice water at high speed for 5

to 10 minutes and filtered in a bag made of closely

woven fabric. The pressed green juice was heated

carefully in a 2-liter Erlenmeyer flask immersed in

boiling water and agitated with a slow motion stirrer. At 550 C, a green coagulum formed and was

separated by centrifugation, washed several times,

and finally spread in thin layers on glass plates and

dried, The supernatant from the centrifugation was

heated carefully to 64° and the white curd

coagulum that formed was separated by centrifugation, washed with acetone, and dried in a rotary

evaporator. The liquid was further heated to 820.

After cooling, a light tan precipitate formed and

was processed as the 640 fraction (see fig. 1),

The spontaneous coagulation of protein in the

juice extracted from some plants was observed during the survey of tropical plants. This phenomenon

occurred during extraction of leaves of cassava,

Leucaena leucocephala; some Indigoferas,

Desmodium, and Mimosa species; and many of the

tree legumes of Mimosa, Cassia, and Pea subfamilies. These plants have been classified as Type I

(table 1). Another group of plants yielded a green

78
Leaf Protein Extraction From Tropical Plants ● 7 9

Table 1 .—Crude Protein Content of Tropical Plants

Amarantlius anclancaluius Hungary 12. 3 26. 6 I v

A. caudatus Sweden 13. 0 27. 7

I v

A. cruentus Taiwan 14.6 28.3 IV

A. gangeticu s Hungar y 14. 5 24.4 Ii’

A. hypochondriacus Sweden 11.5 27.9 Iv

A. mantegazzianus Sweden 16.2 30.0 IV

COMPOSITAE

11

Helian thus uniflorus 11

H . annuus

Hungary

Sweden

29. 9

25. 4

CRUCIFERAE

Hungary

Pakista n

Guatemala

Yugoslavia

Poland

Hungary

France

China

22.5

14.2

10. 8

10.4

12. 6

11. 8

11. 6

14. 4

13. 8

12. 2

14. 2

10.2

10. 8

14. 1

14. 0

12. 6

12. 3

18. 2

39. 8

19. 1

21. 0

30. 0

30.8

21. 1

26. 4

24. 4

27. 1

22. 3

24. 8

26. 4

24. 0

20. 6

19. 4

19. 4

17. 6

22. 6

I I I

I I I

I I I

I I I

111

111

I I I

I I I

Brassica alba

B . campestris

B. hirta

B. napu s

Brassica juncea India

Cuba

Nepal

Ind i a

Turkey

C r eec e

United States

United States

Puerto Rico

Puerto Rico

B. nigr a

B. olerace a

B. “ var. gongyloides

Lepidium sativum

Nasturtium officinal e

CUCURBITACEAE

Indi a

S. Afric a

Indi a

18. 0

11. 4

19. 3

18. 0

26. 3

26. 3

11

I I

I I

Benincasa hispid a

Lagenaria sicerari a

Luffa cylindrical

EUPHORBIACEAE

Cnidoscolus chayamansa

Manihot esculenta

Mexico

Colombia

18. 8

20. 8

26. 3

25. 5

11

I

LECUMINOSAE

Aeschynomene falcata

A. scabra

A. indic a

Brazi l

Mexico

Indi a

20. 2

20. 8

20. 8

13. 5

15. 5

16. 9
80 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Alysicarpus vaginal is

Cajanus cajan

Calopogonium muconoides

Canavalia ensiformis

C. gladiata

Centrosema pubescens

Clitoria ternatea

Crotalaria alata

C. argyrolobioloides

C. brachystachya

C. incana

C. juncea

Cyamopsis tetragonoloba

Desmodium canum

D. distortum

D. intortum

D. perplexum

D. sandwicense

Glycine wightii

Indigofera arrecta

I. brevipes

Y-. cireinell a

T-. colutea

I. confusa

TA. cryptantha

I. echinata

X. hirsuta

I. hochstetter i

I. microcarpa

I. mucronata

I. recroflexa

I. schimperi

I. semitijuga

I. spicata

I. subulata

I. suffruticos a

I. sumatrana

I. tetlensis

I. Ceysmannii

I. tinctori a

India

Ceylon

India

Mexico

Indonesia

India

Brazil

Philippines

India

Philippines

Ivory Coast

Brazil

Cuba

Australia

India

Kenya

Brazil

Argentina

India

USSR

India

Brazil

Hawaii

Spain

Brazil

Brazi l

Australi a

S. Afric a

Chana

Costa Rica

Korea

S. Africa

Australia

Indonesia

S. Africa

Tanzania

Nigeria

Brazil

Rhodesia

Rhodesia

Argentina

Peru

Brazil

Kenya

Africa

India

Tanzania

Kenya

Cuba

Brazil

Mexico

Australia

Africa

Malaya

Dem. Republic

20.1

18.6

24. 0

2 .0

20. 0

21. 5

19. 8

20. 9

23. 5

25. 0

20. 0

16.1

20. 6

19.2

18. 6

20.4

19.2

19. 3

21.4

24. 0

14.2

20.8

16. 8

25. 0

25. 0

20. 0

21.7

19.2

31.2

18. 3

17. 6

16.4

20. 2

19. 8

19. 8

21. 0

22. 1

21. 0

23.4

18. 3

34.9

20. 8

23.7

21. 8

14. 6

31.8

16.5

27.2

26.4

21.4

20.7

21. 8

20.2

21. 6

20. 6

20.0

20.3

22.5

20.6

19.7

18.4

22.1

21.9

18.9

23.2

19.4

23.6

23.0

24.3

19.9

23.9

27.4

22.9

25.8

26.3

19.2

18.9

17.8

18.7

23.5

16.2

23.0

19.6

15.1

26.8

26.2

28.1

28.7

14.6

24.0

21.4

24.2

27.9

30.6

21.2

22.3

22.4

24.4

21.2

23.3

17.2

35.7

12.3

10.8

25.3

32.4

28.2

20.5

31.0

15.2

111

I II

111

111

111

111

111

111

111

111

111

111

111

III

II

II

11

II

11

II

I II

I.

111

III

111

11

1

I II

II

II

I

I.

I II

11

111

II

11

II

II

II

II

II

11

11

11

II

11

II

II

11

11

II

I II

11

11
Leaf Protein Extraction From Tropical Plants ● 8 1

Lablab purpureus

Lupinus albus

L. angustifolius

L. luteu s

L. hispanicus

Macroptilium lathyroides

Macrocyloma uniflorum

Mucuna deeringiana

Phaseolus acontifolius

P. calcaratu s

Psophocarpus tetragonolobus

Sesbania arabica

S: cannabina

S. exasperate ’

S. macrocarpa

S. sesban

Stizolobium aterrimum

Stylosanthes gracili s

S. humili s

Tephrosia adunea

T. cinerea

T. incana ‘

T. noctiflora

T. vogelii

Vigna mungo

V. radiat a

V. unguiculata

Zornia brasiliensis

Z. diphylla

Z. latifoli a

MALVACEAE

Abelmoschus manihot

SOLANACEAE

Capsicum annuum

Malaysia

Turkey

Hungary

S. Africa

Hungary

Spain

Portugal

Spain

Australia

Puerto Rico

South Africa

Mozambique

India

Afghanistan

Ivory Coast

Honduras

Puerto Rico

Turkey

Afghanistan

India

Brazil

Argentina

Australia

Mexico

India

China

Mexico

Paraguay

Australia

Brazil

Venezuela

Uruguay

Kenya

Indonesia

Brazil

Puerto Rico

Pakistan

China

Iran

Turkey

India

Guatemala

Mexico

Brazil

Brazil

Brazil

Japan

Yugoslavia

21.5

18.8

20.4

22.6

22.2

20.4

20.6

20.2

18.8

18.6

21.0

17.2

18.8

22.2

19.7

20.1

20.6

21.8

22.2

19.8

20.4

20.6

22.0

19.8

20.6

19.4

20.6

21.2

22.0

21.8

22.2

24.2

23.8

24.4

23.6

20.4

19.3

21.0

19.3

18.9

21.1

18.8

19.0

20.2

19.8

20.0

14.6

20.0

27.7

19.5

18.8

16.6

16.1

19.2

19.8

19.2

19.5

26.4

21.3

32.6

18.3

15.8

20.8

23.7

22.0

29.9

30.0

21.4

20.9

20.6

19.2

19.9

27.6

29.4

27.4

22.3

20.9

18.9

18.0

14.0

19.3

21.4

13.2

12.3

23.6

24.0

16.9

22.9

22.2

19.5

19.4

15.8

16.8

15.8

14.0

22. 4

I II

111

111

I II

I II

I II

I II

111

I I I

I II

I II

11

111

111

111

111

I II

111

111

111

111

I II

I I I

111

111

111

111

IV

IV

Iv

11

11

II

II

II

II

I I I

111

111

111

I II

111

111

I II

111

111

111

111
82 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

—

Capsicum annuum Ecuador 12. 5 19.9 I II

Israel 20.0 21.8 111

C. chinense Ceorgia-USA 15.3 20.0 111

Guatemala 15.3 23,.4 111

Colombia 16.7 19.9 111

C. pendulum Mexico 18.0 19.8 111

Chile 22.2 21.0 111

California-USA 16.0 20.2 111

Solarium melongena India” 21.0 21.2 I II

China 21.4 21.4 111

a Yield of different, fractions after extraction: I. Only one green fraction coagulated at

room temperature: 11.’0ne green fraction on heating to 55°C and one minute amount of light tan

fracticln at 82” ; III. One green fraction at 55°. one white fraction at 64” and another light

can fraction at 82°; IV. No distinct separable coagulum by heat fractionation.

SOURCE: Telek(77)

Figure 1.— Laboratory Method for Preparation of Protein Concentrate From Tropical Plants

FRESHLY HARVESTED

PLANT

Macerate

Press

PRESSED GREEN

CROP JUICE

I Heat 55° C

Precipitate

Heat

r

Centrifuge Heat

Liquid

Centrifuge

Precipitate Liquid

I I .

DEPROTEINIZED

JUICE

Centrifuge

82”’

v

Solids Solid

Or Dry

GREEN PROTEIN WHITE PROTEIN12(ITEIH

SOURCE:Telek(77)

protein coagulum after the extracted green plant fractionation of

juice was heated to 55°C and yielded a very small distinct protein

Solid

aqueous leaf extracts yielded three

fractions: a greencoagulumat550

quantity of a light tan precipitateat820 C. This first C, a copious white protein precipitate at 64° C, and

was observed with leaf protein extract of sorghum- a smaller amount of a light tan precipitate at 820

sudan grass hybrids and other grasses. Plants of this C. The most desirable plants for further studies

group have been classified as Type II. Type III is were selected from this group (table 2). A final

the most important group of plants. Careful heat group, designated as Type IV, includes plants in
Leaf Protein Extraction From Tropical Plants . 83

Table 2.—Selected Plants for Leaf Protein Concentrates Production

- — — -- .

% Protein % Biologica l

Dry metter yield of dry Mg/he/year protein nitrogen

Plants ma t t e r extractability fixation Regrowth

Brassica napus

Centrosema pubescens

Clitoria ternate a

Desmodium distortum

Lablab purpureus

Macroptilium lathyroide s

Psophocarpus cetragonolobus

Sesbania sesban

Vigna radiata

V. unguiculata

28

12

28

11

19

12

20

20

16

25

SOURCE:Telek(77).

25.4

18.8

24.0

18.0

28.4

26.0

22.2

28.6

22.9

19.5

62.4

37.2

59.8

47.9

58.1

59.0

53.6

40.2

47.8

52.0

+

+

.+

+

+

+

+

+

+

Poo r

Good

Good

Good

Good

Good

Fair

Fair

Fair

Fair

which the proteins in the aqueous extracts do not

precipitate either spontaneously or after heat treatmerit. This was observed in extractions of Stylosanthes gracilis, S. humilis, Nasturtium officinale, and

Amaranths spp.

Pilot Plant Scale Preparation and

Nutritional Evacuation

Leaf protein concentrates from the tropical legumes Leucaena Zeucocephala, Vigna unguiculata,

Clitoria ternatea, Desmodium distortum, Psophocarpus tetragonolobus, Macroptilium lathyroides,

Phaseolus calcaratus, Brassica napus, and Manihot

esculenta were prepared on a pilot plant scale. The

plants were harvested in the vegetative stage of

growth, stored in a freezer, transported in a frozen

state, and processed in the pilot plant of the Food

Technology Laboratory, University of Puerto Rico.

Processing consisted of chopping to 2-cm pieces

followed by soaking in 2-percent sodium metabisulfite, The soaked material was disintegrated in

a hammer mill and pressed in a single-screw press.

The expressed juice was heated with steam to 820

C until a protein coagulum appeared. The hot

coagulum was collected in a basket centrifuge,

pressed in a canvas bag under a hydraulic press,

spread in a thin layer on glass plates, and dried

in an air-conditioned, dehumidified room. The

pressed green juice of Leucaena leucocephala and

cassava was left for 20 hours for self-precipitation

of proteins at ambient temperatures (290 to 310 C).

The settled precipitates were processed as outlined

above.

The protein quality of the LPC was evaluated by

using rats (17). The tropical legumes Vigna unguiculata, Desmodium distortum, Phaseolus

calcaratus, and Psophocarpus tetragonolobus gave

excellent results, comparable to those obtainable

from alfalfa LPC. These plants have low polyphenol

contents. Another legume low in phenols, Macroptilium lathyroides, gave relatively poor results [table

3) due to its high saponin content. The differences

in rat growth probably are due to different amino

acid availabilities, as influenced by polyphenols and

other compounds that may react with protein to

form indigestible complexes.

The LPCs from the tropical legumes tested were

found to have amino acid contents similar to each

other and to reported values for alfalfa LPC and soybean meal (table 4).

Cassava and Leucaena were included in this nutritional evaluation, alongside the selected plant

sources, to support our classification of plants

based on the number of protein fractions. It was

suspected that the spontaneously precipitated protein concentrate from Type I plants would have less

nutritional value. Rats fed LPC from cassava and

Leucaena grew poorly. The data showed that protein concentrates from these plants cannot be produced by the accepted LPC processes.

About two decades ago, the use of tree leaves as

a potential source of leaf protein concentrate was

suggested (60,64), and their possible use is still being mentioned in literature, The presence of phenolic substances negatively affects the nutritional

value of the proteins prepared from tree leaves.

After our studies of Leucaena leucocephala, we extended our investigations to the other tree legumes

located in Puerto Rico. The Leguminosae family is

huge (14,000 species) and extremely diverse, ranging from forest trees to shrubs to herbaceous

annuals.

The results of our investigations, given in table

5, clearly indicated that, with current methods,
84 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Table 3.—Protein Content of Tropical Plant LPC, Diet Composition, and Rat Growth Performance

Diet Composition

Crude

Protein

(:~cff z

Source of LPC L:C Corn

Corn-soy control

Leucaena 1 eucoce hala

k%%:m:%:!ed)

~nihot esculenta 3

t4. escul enta’

~ escul enta 3

~ esculenta (acetone-washed)

J!W!!! Unguiculata

Cl i toria ternata

Desmodium distortum

D. distortum (acetone-washed)

~ophocarpus tetragonolobus

Macroptil ium lathyroides

Phaseolus calcaratus

Brassica napus CV. Early Giant

----

31.3

38.2

28.2

36.2

32.1

33.3

41.4

51.9

59.3

36.5

47.0

51.9

44.6

38.0

40.4

----

31.9

26.1

35.5

27.6

31.2

30.0

24.2

19.3

16.9

27.4

21.3

19.3

22.4

26.3

24.8

69

57

64.5

52.7

62.6

58.1

59.6

66.8

71.7

74.1

62.8

69.7

71.7

68.6

64.2

66.1

z

soybean

Heal

Rat Performance

Avg. Avg.

22:

0 . 4

2.8

0 . 8

1.7

1.4

---

---

---

0.8

---

---

---

0.5

0.1

Avg. Dai iy Daily

Da i 1

x

Gain Feed

Gain as Z of I ntake2

9) Control 9)

7. z? .4f 100 16.411.5

0.92. 4: 12.5 11 .O~l .8

0.72.1 11.6~1.9

l.of.gh 1?:; 9.7*1.4

1.8f.2gh 25.0 11.72 . 9

2.0?.59: 27.8 11 .121.2

1.22.39 16.7 11 .721.9

2.0:.4~h 27.8 14.811.7

5.8f.9f 80. 6 18.221.8

6.72.4 93.1 17.7*1.6

5.4~1.of 75.0 73.021.1

6.6t.9f 91.7 16.6~2.O

6.0fl.0f 83.3 17.2=1.3

3.02.57 41.7 14.9~2.O

&()?.6f 83.3 13.5~1.2

6.12.9 84.7 17.4tl.5

Protein

Efficiency

Ratfo

‘N X 6.25

~~an ~ standard deviation.

Means followed by different

letters differ at p 0.01. ~Dried in microwave oven.

● Dried in air-conditioned room.

SOURCE: Cheeke(17).

good quality leaf protein concentrates for nonruminants could not be prepared from many of the leguminous tree leaves, especially those of Type I

plants. However, some of the leaves of the Leguminosae definitely could be used as feed for ruminants after careful analysis for toxic ingredients.

Stylosanthes humilis and S. guianensis offered

promise for leaf protein extraction. These valuable

pasture plants are perennial legumes with high DM

yield and a protein content that is as high as that

of alfalfa. However, during maceration of these

plants, a thick emulsion formed which could not

be separated from the fibrous material either by

centrifuging or by pressing. On heating, the emulsion thickened and separation became even more

difficult. After unsuccessful processing experimerits with 10 different cultivars, further research

was abandoned.

The lush vegetation of the humid tropics is often

considered to have a high potential for animal production. The grasses are an extremely large family

of more than 10,000 species, Tropical grasses have

a capacity for photosynthetic high rates, grow year

round, and show excellent regrowth after repetitive

cutting. However, the natural nitrogen (N) content

of grasses is relatively low and heavy nitrogen fertilization is required for high DM production.

Our experiments with forage sorghum (Millo

Blanco) and sudan hybrids showed encouraging

yields (71), However, the extractions were disappointingly low: 28.6 percent extractable protein

compared with 52.4 percent for legumes. Investigations of tropical grasses as sources for leaf protein

extraction were suspended. It was concluded that

the ever-increasing cost of nitrogen fertilizer, the

higher processing costs due to lower crude protein

content, low extractability of tough fibrous plant

material, higher energy requirement of the disintegrator, and the lower quality of protein would make

the process uneconomical. With a low initial N content, the extraction of protein from grasses could

reach the point where the pressed residue, the most

important byproduct, could not be used by ruminants.

Our relatively short systematic investigation of

possible tropical plant sources for leaf protein extraction and fractionation produced the following

valuable results:

1, Plants equivalent to alfalfa in yield, extractability, and nutritional quality were selected,

2. It was recognized that in the Tropics a single

crop cannot be used for year-round production; a pattern of different plantings has to be

formulated for rainy and dry seasons. Hello
Leaf Protein Extraction From Tropical Plants ● 8 5

——. —

Leucaena

Table 4.—Essential Amino Acid Composition of LPC From Tropical Species

gm amino acid/100 g recovered amino acids

Source of L P C A r g His t I so I Leu Lys Meth Phe Thr Val 1/2 cyst

leucocephal a 6.4

Manihot esculentaa

Manihot esculentab — —

Vigna unguiculata

Clitoria ternatea

Desmodium distortum —

Psophocarputs tetragonologus

Macroptilium lathyroides

Phaseolus calcaratus

Brassica napus

Medicago astivac

6.3

6.0

6.7

6.1

6.1

6.2

6.6

6.0

6.2

6.5

2 . 2

2.4

2,4

2,4

2,2

2.6

2.6

2.5

2.5

2.6

2.3

a Dried in air conditioned room .

b Dried in microwave oven.

c Iiuzmich>’ and KollJer (1!177) .

SOURCE: Cheeke (17),

5.0

5,4

5.2

5.4

5.8

5*5

5.4

5.6

5.4

5.3

5.6

3.

4.

and Koch’s (32) statement that “When it is

possible to use the raw material of one or only

a few plant cultures—e. g., in tropical regions,

the technological problems are not as great”

now seems inaccurate.

Our studies seriously question the popular belief that cassava, Leucaena leucocephala,

other tropical tree leaves, and tropical grasses

are potential sources of LPC.

The protein pattern, or number of protein

fractions obtained by heat fractionation, was

discovered to be a rapid preliminary method

to screen plants for protein extraction potential. Type I plants have a low probability of

yielding good LPC.

Machinery of Leaf Protein

Fractionation

The development of economical equipment for

successful farm-size leaf protein processing is a major task. Hjalmar Bruhn (14), a leading authority in

the United States on farm machinery designed especially for protein extraction wrote: “I don’t see

9.1

4,3

9.1

9,4

9.1

9.4

9.3

9.7

9.2

9“. 3

9.3

6.3

6.5

6,4

5,8

6.1

6.5

6.4

5.4

6,4

5.8

5.9

2.4

2.5

2.4

2.7

2.4

2.6

2.5

2.7

3.0

2.6

2.3

5.9

7.0

6,8

7*5

7.2

7.3

7.1

7.5

7.1

7.5

5.9

4.8

4,9

5.2

5.3

5.2

5.0

5.2

5.0

5.1

5.3

5.1

6.0 0,7

6.0 0.8

5.7 0.7

6,4 0.6

6.2 2.0

6.0 0.6

6.4 0.6

6.4 0.6

6.2 0.7

6.4 0.7

6.3 0.6

much hope for any appreciable protein production

unless there are well engineered machines that are

commercially available at farm machinery prices. ”

The separation of plant juice from the fiber is a

two-step process: The rupture of the plant cells by

maceration and the separation of the juice and

fiber. Cell rupture is the most energy intensive process in leaf protein extraction.

Macerating

Initially, macerating sugarcane rollers were used,

but such equipment proved to be ineffective, The

overall capacity was low when operating under

higher pressure, the power requirement was high,

and the machine was very heavy for portable farm

use.

Varying degrees of cell disintegration can be accomplished by hammer mills of different construction. These should be used when a high percentage

of protein is to be extracted, when the initial plant

material has a high protein content, or when the

pressed crop will not be used as forage for cattle.

The evolution of small equipment designed in

Rothamsted Experimental Station in England
86 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Table 5.—Protein Content of Leaves of Tropical Legume Trees

% Plan t

Protei n type

1 Cassia . Subfamily (Caesalpinioi

Bauhinia alba . . . . . . . . . . . . . .

Bauhinia candida . . . . . . . . . . . .

Bauhinia galpini. . . . . . . . . . . .

Bauhinia purpurea. . . . . . . . . . .

Bauhinia reticulata. . . . . . . . .

Bauhinia violace a . . . . . . . . . . .

Cassia moschata. . . . . . . . . . . . .

Cassia nodosa. . . . . . . . . . . . . . .

Cassia spectabilis. . . . . . . . . .

Delonix regia . . . . . . . . . . . . . . .

Libidibia punctata. . . . . . . . . .

Tamarinds indica. i...... . . .

2. Mimosa Subfamily (blimosoideae)

Albizia adinocephala... . . . . .

deae)

17.43

13.20

16.22

8.9 2

12.59

11.80

6.47

8.58

14.24

22.85

25.90

10.57

14.89

10.03

20.80

14.77

16.60

Enterolobium cyclocarpum. . . . 26.58

Inga laurina . . . . . . . . . .

Inga Vera. . . . . . . . . . . . .

Leucaena leucocephala.

Parkia biglandulosa. . .

Pithecellobium dulce. .

Samanea sampan . . . . . . .

. . . . . . 18.34

. . . . . . 21.44

. . . . . . . 26.80

. . . . . . 12.85

. . . . . . 18.43

● . . . . . 17.41

3. Pea Subfamily (Faboideae)

Dalbergia sissoo. . . . . . . . . . 12.9 1

Erythrina poeppigiana.. . . . 19.1 3

Erythrina variegat a

orientalis. . . . . . . . . . . . . 17.9 4

Myrospermum frutescent. . . . 19.4 2

I

I

I

I

111

I

111

I

111

I

I

I

I I I

I

I

I

I

I

I

I

111

111

111

I I I

111

111

SOURCE: Telek, unpublished.
Leaf Protein Extraction From Tropical Plants ● 8 7

— —

before 1960 has been published by Davys and Pirie

(19). Later, to standardize processing methods, new

equiment was built and evaluated in several countries. The new pulper contains 58 fixed beaters with

2 mm clearance from the drum. The rotor is driven

by a s-horsepower (HP) motor. Field experimentation has shown that units can be mounted on a

Landrover whose engine drives the pulper. The

standard model takes 1 kg crop/rein, but could be

increased to 6 kg/rein. The capacity to macerate 360

kg/hr makes this pulper useful at the village production level (61).

The large-scale fractionation machinery at the

National Institute of Research on Dairying (NIRD),

Shinefield, England, was developed from a design

of Davys and Pirie (20). The pulper has 32 arms that

rotate in a cylinder and are driven at 1,100 rpm by

a 32.3 HP motor. The total power requirement is

6 to 8 kilowatt hours per metric ton (kWh/MT) of

initial crop. More powerful disintegrators of this

type were built for the large industrial process.

These machines will not be discussed in detail,

since they are not related yet to tropical production.

The most energy efficient way to macerate at high

capacities is by using extrusion, where the plant

material is forced through an orifice (50). High capacity rotary extrusion macerators have been designed by Basken (5) and Nelson, et al. (56). These

macerators consist of an internal roller operating

against a die ring perforated by radial orifice holes.

One of these experimental macerators operated

with 22.1 MT/hr capacity at a power input of about

1.7 kWh/MT (fig. 2).

Pressing

The performances of the double screw, single

screw, and belt presses used in leaf protein preparation in British research and a commercial crop drying plant were evaluated by Shepperson, et al. (68).

Screw presses are effective machines for removing

juice from the macerated forage, but their energy

consumption is higher than that of some other press

designs due to rubbing and shearing action in the

press. industrial screw presses are expensive and

less suitable for mobile installation (fig. 3). Platen

presses have been used in small or medium installations and can have a capacity of 1.8 to 3.6 MT/hr.

The power consumption is low. Belt presses were

found to have limitations in the forage dewatering

process because maximum pressure is limited by

the nature of belt tensions. If new synthetic belts

could be produced, this system could be built as relatively light equipment. Several presses for LPC

production were described by Pirie (61) (fig. 4). A

Figure 2.— Rotary Extrusion Macerator

Photo credit: Courtesy of H. D. Bruhn and R. J. Koegel

Figure 3.— MINIPRESS Ml IB.

Photo credit: Courtesy of N W Price

commercially available cone press was evaluated

by Koegel, et. as. (51) and gave satisfactory results

for final moisture content and energy requirement.

A new press was designed with a capacity to press

16.5 MT/hr of freshly macerated material to a final

moisture content of 65 per cent or less. The weight

of the press is 3.1 kg. The results of the evaluation

of the cone press for forage fractionation were reported by Straub and Koegel (73), who suggested

some changes in cone rotation speed. The average

total energy required for the press was low; 0.95

KWh/MT. The sum of energy requirements for

macerating alfalfa and pressing it in the cone press

is about 3.25 kWh/MT (Nelson et al, 1981). Energy
88 . Plants: The Potentials for Extracting Protein, Medicines, and Other Usefu/ Chemicals—Workshop Proceedings

Figure 4. —Cone Press

Photo credit: Courtesy of H. D. Bruhn and R. J. Koegel

requirements for maceration and pressing of freshly harvested forage are compared in table 6.

Professor Bruhn (14) converted meat grinders

into good, medium, and miniature size systems for

laboratory evaluations to replace Waring blenders

(fig. 5). The high-speed electric blenders do not

duplicate industrial crushers; they chop the fibers

into small particles, which will be mixed into the

green leaf protein concentrate during the heatcoagulation process.

Separation of Protein Concentrate

Juice, if not directly fed to animals, should be

processed without extensive delay. Separation of

protein is accomplished by several methods (table

7); however, the most convenient is coagulation by

steam injection. An automatic system was developed by Straub, et al. (75), to coagulate the juice and

separate the coagulated protein from the brown

juice. The incoming juice was preheated by a heat

Table 6.—Energy Requirements for Producing Leaf Protein Green Juice

Process hp/h/to n Referenc e

Field harvestin g

Direct cut and cho p

Maceratio n

Extrusio n

Roll crushin g

Hammer milling

Hammer milling

Pressing

Screw press

Roll press

High-cycle plate n

Cone

SOURCE: Compiled by Telek, 1983

3 - 7*5 1 - 2.5 ASAE Yearbook, 1975

7.5 - 30 2.5 - 10 Basken et al., 1975

15 - 90 5 - 30 f?

42 - 150 15 - 50 11

16.5 5.5 Carroad et al., 1980

6- 3 0

15 -30

15 - 30

---

2 “- 10 Basken et al., 197 5

5 -10 t?

0.5 - 1 ?t

1.14 Bruhn and Koegel, 1982
Leaf Protein Extraction From Tropical Plants ● 8 9

—

Figure 5.— Rebuilt Meat Grinder as Miniature Screw

Press

Photo credit: Courtesy of H. D. Bruhn

JUIC E

Table 7.—Separation Methods of

Treatment

HEATING not measured

80°-840 C

60°and 84°

55° , 64° , 82°

exchanger, salvaging the heat from the brown juice.

The generally accepted energy requirement is 50

kg of steam/MT green crop.

Low-cost and simple technology systems for leaf

protein separation and recovery using on-farm level

operations have been reviewed by Straub, et al. (74).

A farm-scale centrifuge designed to separate suspended solids from animal waste was evaluated. It

had a slower than expected acceleration rate and

the through-put rate was low: 5 kg/rein. Other systems were designed based on flotation, consisting

of a stainless steel tank (0.25 m x 0.36 m x 2.64 m)

with a working capacity of 211 liters and a built-in

steam injector. The flow rate was 42 l/rein with a

hold time of approximately 5 minutes for flocculation in the tank. The mechanical skimmer was rotated at a speed of 2.3 m/min, and the paddles were

immersed in the tank to 5 cm below the spillway

(fig. 6).

The belt filtration system consisted of an 8.5-m

long continuous woven polyester belt with a variACID

ORGAN I C

SOLVENTS

ethanol

acetone

n butanol

ANAEROBIC

FERMENTATION

LPC From Green Juice

Fractions

green and whit e

gree n

green and whit e

green and two white s

gree n

gree n

gree n

green

green

Reference

Rouelle, 1773

Pirie, 1971

Edwards et al. , 197! — .

Telek, 1979

Pirie, 1971

Huang, 1971

All i son, 197 3

i n Hove and Bailey,

197 5

Stahman, 197 8

Anelli et al ., 197 — 7 .

Knuckles, 198 0

SOURCE: Compiled by Telek, 1983

24-503 0 - 83 - 7
90 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

 ——-..—..——— ——— —

Figure 6.— Flotation Separator

HEAT EXCHANGE R

1

1

PLANT

JUICE

SUPPLY

I sv2 T V2

I STEAM.

SUPPLY

Sv1 T V1 T V3 Q C V

I I I I I I

SKIMMER

I I I I I

STILLING TROUGH ,

\

S 3

Plant Juice Protein Processing System Controls

Symbols: CV - Check Valve s - Sump

- Solenoid Valve T - Temperature Sensor

TV - Throttling Valve VR - Vacuum Release Valve

p - Pump QCV- Quick Closing Valve

SOURCE: Straub, et al, (75).

able moving speed of 3.0 to 15.2 m/min. (fig. 7). The

belt filter was fitted with a 0.25-m long x O, S-m x

0.3-m tank to allow for flocculation of the juice protein. This provided an average 1- minute hold time

for the heat treated juice prior to being spilled onto

the traveling belt by a paddle wheel assembly which

rotated at a rate of 20 rpm. There was an initial free

drainage section on the belt. This was followed by

a vaccuum box dewatering section. The material

then was scraped off to pans by a spring-loaded

doctor blade (fig. 8). The evaluation of this process

showed that flotation provides good recovery. However, the protein concentrate was dilute; it was less

than 12 percent solids. The filtration provided moderate levels of solids, but had poor recovery rates.

Use of flotation as pretreatment to belt filtration

provided improved recovery and moderate solid

concentration. Mean solid levels of proteins separated by various methods are shown in table 8. The

results using this relatively complex machinery are

somewhat disappointing, and further refinement is

needed. In an on-farm operation, such as hog raising where a wet product can be used, this solid level

would be acceptable. The protein concentrate could

be mixed with barley or cassava chips for immediate use or partly extruded and sun-dried for short

duration storage.

LPC Extraction at Village Level

The most basic application of leaf protein fractionation is at the village level. The operation is simple. Production should be geared to consumption

by farm animals to avoid preservation and storage

problems, The system, using the pulper and press

developed at Rothamsted Experiment Station,

England, and purchased by donors, has been

studied in Pakistan (66), India, and Sri Lanka.

In a rural resettlement of people from urban

slums in Pakistan, a trial has been suggested to testmarket LPC produced by this machinery for dairy
Leaf Protein Extraction From Tropical Plants . 91 —

●

●

n

w

I 1 I al

n

I I 1

n n

I I I

c
COACULATION

TANK

SOURCE: Straub, et al. (74)

Figure 8.— Belt Filtration

Photo credit Courtesy of F/. D. Bruhn and R. J. Koegel

cattle and green LPC for local sale. The labor force

would be recruited from the resettled families

under the supervision of trained personnel.

Indian and Pakistani scientists are cooperating

in the leaf protein work. Dr. Shah of the Pakistan

Council of Scientific and Industrial Research visited Mysore, Coimbatore, and Aurangabad to learn

of the Indian progress in implementing village-level

LPC production.

The work in Aurangabad, India, is the most relevant to practical application of any in progress. It

DOCTOR BLADE PROTEI N

Q )

attempts to establish a commercially viable LPC

production unit at a village farm, using a simplified

screw press that Pirie (62) has been developing for

a number of years (fig. 9).

This press accomplishes both cell rupture and

juice expression in a single press. A similar unit

was built in the workshop of Marathwada University. The press is driven by a 3-HP motor. The juice

is drained over a vibrating screen, then precipitated

in a thermostatically controlled oil bath. The coagulum is filtered through cloth stockings (fig. 10).

The locally constructed equipment could be scaled

up according to need (18).

Joshi, et al, (42), reviewed the prospects and problems of leaf protein production on a small farm in

Bidkin, an Indian village about 25 km from Aurangabad. The green protein concentrate made from

alfalfa was used as a milk replacer for calves, a s

poultry feed, and as human food. The pressed crop

was remixed with solubles and fed immediately to

cows. They accepted the material willingly, however, they rejected it when offered it the next morning. Equipment and a dairy unit of 5 to 6 cows

would cost at least $4,450 (Rs 35,500*), an excessive

expenditure for a small farmer. Joshi suggested that,

in the immediate future, both of the products of

green crop fractionation be sold in the market. This

project was supported by the Meals for Millions

Foundation, and its economics were evaluated by

Bray (13).

A flow chart for the process is shown in figure

11. After the crop is pulped, it is pressed to yield

green juice and fiber. Heating the juice yielded 25

“’1’he exchange rate of the Indian rupee (Rs) is calculated at

KS 7.8 I)er $U. S.
Leaf Protein Extraction From Tropical Plants ● 9 3

Figure 9.-Simplified Screw Press

Photo credit: Courtesy of N W. Pirie

Figure 10.-Screw Press Designed and Built in Aurangabad, India

MOTOR REDUCTION UNIT HOPPER FRESH CROP SCREEN

SOURCE Courtesy of R. N. Joshi

COAGULUM
94 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals— Workshop Proceedings —

Figure 11.— Process Flow Chart of Leaf Protein Fractionation on Village Level in India

Cut and Pulp

Green, Juice

Purify

I

I

I

I

I

Separate- Protein ~

SOURCE: Bray (13)

kg LPC from about 1 MT of freshly cut alfalfa. In Equipment Costs

a-variation of this process, the pulped crop is extracted with the solubles from the protein precipita- The cost for both processes was calculated at

tion phase, to yield an enriched fiber fraction for about $3,200 (table 9).

feeding ruminant animals. The leaf protein concentrate—containing 60 to 65 percent protein, 22 to 24 Land

percent lipids, and carotenoids (pro-vitamin A)–

could be consumed by people or nonruminant ani- Since the extraction process requires about 1 MT

reals, or used as a milk replacer for calves. The in- of fresh alfalfa per day, the produce from about 2

put requirements for this process are indicated ha would be needed to keep it operating continubelow. ously.
Leaf Protein Extract/on From Tropical Plants ● 9 5

—

Wash Tank

Cutte r

Pulpe r

Dewatering pres s

Juice pump

Liquid Cyclon e

Waste Receive r

Holding Tan k

Heater/Coagulato r

Curd Filte r

Beam Press

Holding Tan k

Mixing/Wash Tanks

Beam Press

Table 9.— Equipment Costs for LPC Preparation

on Village Level in India

Rs 1500

1540

5500

4500

116 0

80

160

1700

100

320

160

Total Cost Rs 18870 ($2,359. )

Installation 25 % 4720

1890

Rs 25480 ($3 ,185. )

SOURCE: Bray (13).

Crop Cost and Income Electric Power

Current costs for alfalfa vary widely. With an ex- The power required is 5.6 kW for pulping and

pected yield of about 100 MT of fresh alfalfa/ha/yr, 6.75 kW for pressing at $0.034 per kWh.

a farmer would receive $1,600, an income higher

than he would get raising other crops. Fuel

Labor Requirements and Salaries The fuel is low quality coal that would cost about

$0.002/kg LPC. The production cost per kg LPC is

For an 8-hr day, the salary of the supervisor is summarized in table 10.

$1.50, $0.99 for operators, and $0.75 for helpers. Suggested retail price for 1 kg LPC would range
96 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

.- — — —

Table 10.—Leaf Protein Production Cost Summary

at Village Level in India

Process 1

Pressing)

Raw material (net cost) Rs 1.02/kg L P C

Labor and supervision 1.72

Power 0.58

Fuel 0.13

Maintenance 0.66

Supplies, etc.

Depreciation

Interest expense

Other fixed charges

Total fixed costs

0.29

Rs 4.40 = 55¢

009 1

0.6 0

0.25

Rs 1.76 = 22¢

Total production cost Rs 6.16/kg LPC = 77¢

SOURCE Bray(13)

from $l,19 (Process 2) to $0.79 (Process l) Leaf protein probably would be incorporated into a final

food product, then sold. For example, in the Coimbatore feeding program, LPC was mixed with cassava flour and sugar and fed to children as a soft

sweet mixture called a laddu. If a similar product

containing leaf nutrient concentrate were to be sold

in the market, it could be priced at $0.50 per kg.

For only $0.025 to $0,03 per day, a child could obtain 50 percent of his daily protein, iron, and calcium and 100 percent of his vitamin A from such

a product.

Conclusions

The following conclusions are drawn from this

study (13):

1. A green crop fractionation/leaf protein unit

could be easily operated in a village.

2. The cost of the equipment is low enough to

be affordable by village cooperatives.

3. On a nutritional basis, leaf protein would be

much less expensive than most of the protein

from grain legumes consumed in the area.

4. An LPC-containing product that would provide 50 percent of the daily protein requirement of a child would be affordable by the majority of the Indian poor.

In Coimbatore, Friesian, and Jersey cows are consuming the pressed crop, and in preschool nurseries children are getting the LPC in laddu, a food

item developed by Dr. Devadas, which consists of

a mixture of leaf protein with jaggery (a crude sugar

made from the sap of a palm tree), cassava flour,

pearl millet flour, and sesame seed molded into soft

balls. It was fed to the children as a snack. The object of her research was to evaluate the nutritive

value of LPC through feeding programs for 600 preschool children for a period of 3 years.

On-Farm Use of LPC

The basic principle of leaf protein fractionation

is that some plants, mostly the Leguminosae, contain much higher levels of protein than are necessary for ruminant nutrition. This protein can be removed without negatively affecting the growth of

animals. On the other hand, nonruminants are unable to digest high contents of cellulose and cannot consume the amount of dry matter required to

satisfy their protein requirements. Using protein

fractionation, plant material can be separated into

one product suitable for nonruminants and another

suitable for ruminants. Experimental proof indicates that the process can double meat production

in a given area (35).

The concept of on-farm use of leaf protein fractionation is that a weather-independent system can

be devised in which the processing takes place on

a farm and at least one of the products is used at

the production site. The ideal situation would be

a combined dairy and hog production farm using

all of the products grown onsite, thus reducing

transportation expenses, storage costs, and spoilage. This approach has been researched in Britain,

Australia, and the United States.

The research team of the University of Wisconsin, under the leadership of Professor Bruhn, contributed the most in developing new concepts in

machinery designs for this system (14). Research

at the University of Wisconsin at Madison has concentrated on development of a weather-independent, on-farm forage harvesting system using a protein fractionation process. After harvesting, the

main product is pressed forage, which can be preserved directly as silage. The prime objective is a

quick reduction in the moisture content of the fresh

forage from approximately 80 to 65 percent, a desirable moisture concentration for proper fermentation in a silo (31). By this process, field losses can

be minimized to about 2 percent, a reduction from

32 percent or higher when the crop is preserved

as baled hay. The pressed residue contains 50 to

80 percent of the dry matter of the original green

crop. It retains 70 to 80 percent of its original protein content, which is substantially higher than that

of sun-dried hays.
Leaf Protein Extraction From Tropical Plants • 97

Use of Pressed Residue

Use of the pressed residue is the key factor in leaf

protein fractionation. The maceration will make the

fibers more digestible by ruminants. In sheep feeding trials, the pressed crop from either alfalfa or

ryegrass was equally effective when fed freshly

pressed or as silage (80,81). In steers fed a perennial ryegrass and Italian ryegrass mixture, the mean

intake of whole and pressed crops was equal, and

there was no significant difference in weight gain

(40). The liveweight gains in cattle fed the pressed

crop of perennial ryegrass were found to be significantly higher than those of cattle grazed on whole

ryegrass ad libitum (35). Other research concluded

that pressed residual can be fed directly to ruminants with as good results as the original nonfractionated plant (59).

Use of the Juice

The DM content of the green juice is low (8 to

10 percent). The isolation of green protein is an expensive process. The most economical use would

be to feed it directly to hogs to minimize storage

and preservation expenses. The green juice contains proteins, carbohydrates, and lipids. Enzymes

present in juice degrade proteins rapidly, especially

during warm days (69), and the soluble carbohydrate fraction ferments in 24 hours (4). Therefore,

the process must be geared to the feeding time of

the animals. Houseman and Connell (34) effectively replaced separated LPC and conventional seed

proteins and dried LPCs by direct feeding of grass

juice.

According to Braude, et al. (11), grass and alfalfa

juice can replace half of the protein supplement

(soybean or fish meal) in the feed of growing pigs.

However, feeding experiments carried out in Wisconsin gave disappointing results. Pigs did not consume alfalfa juice even when their drinking water

was withheld.

The most economical method for isolating proteins from green juice would be by anaerobic fermentation (1,49,72). Bacteria normally present on

leaves fermented juice samples of many different

plants (alfalfa; corn; oats; pangola, elephant, brome,

and sudan grasses) in sealed containers. The initial

pH of 5.5 to 6.0 dropped to 4.5 after 48-hour fermentation. Amino acid analyses of the fermented and

spray-dried juice protein showed that it contained

40 percent more cystine and 12 percent more methionine, The protein yield was 11 percent lower than

that prepared by heat precipitation. However, pigs’

acceptance of feed containing the fermented product, especially in high proportions, was always low.

An important need exists for animal nutritionists

to convert the fermented LPC product into a palatable swine feed.

In contrast to the village use concept stressed for

LPC research, a serious investigation of process development for commercial LPC production was initiated in 1967 at the Western Regional Research

Center of USDA in Berkeley, California. A large

number of papers have been published on every

phase, including use of the different products. A

highly mechanized process evolved which is covered by several patents (8,10), Several reviews

describe the development of the Pro-Xan process,

the commercial production method for obtaining

leaf protein concentrate from alfalfa (22,23,52).

Figure 12 describes the flow sheet of the process.

The original process has undergone several

changes. Energy saving and pollution reduction

were the main targets of process research; improved machinery was selected to accomplish these

goals. The economies of producing Pro-Xan were

studied by the USDA Economic Research Service

and updated after major process changes (28,82).

The first commercial application of the Pro-Xan

process was by France Lucerne, the largest producer of alfalfa dehydrators in Europe. The first

pilot plant was constructed next to a dehydrator

and produced 2 MT/day of green protein concentrate. In this process the pressed residue is added

to the pelleted, dehydrated alfalfa. Also, the concentrated solubles are recycled to the pelleting

operation. The success of the operation lies in the

central location of the plant in Champagne, the

largest alfalfa growing region in France; its wellorganized sales operations; and the barge canal,

rail, and highway connections available for shipping its products economically. A larger plant was

completed in 1981 and 7,000 MT of green protein

concentrate Pro-Xan are being produced yearly.

France annually produces 900,000 MT of dehydrated alfalfa. Sixty percent of this is produced and

marketed by France Lucerne in Champagne.

Alfa-Laval and France Lucerne agreed to sell two

600 MT/day production plants to the Soviet Union.

The process is based on Pro-Xan technology modified by France Lucerne using alfalfa as plant

material (3).

In conventional dehydration, alfalfa containing

20 to 22 percent dry matter is chopped, transported

immediately to the plant, and dehydrated to 90 to
98 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings —

CHOPPE D

ALFALFA

Figure 12.—The Pro-Xan Process used by the Valley Dehydrating Co.

I . — J

I - STEA M

SOLUTION .

SOURCE: Edwards, et al (25)

92 percent dry matter in the rotary drier. This process generally produces a product higher in protein

content than hay or silage produced from the same

field, without the losses occurring during hay making and ensiling. Dehydration is less weather dependent than the other forage conservation techniques and is highly mechanized. The final dehydrated product is generally in the form of pellets

which can be easily handled.

In the United States, the production of dehydrated alfalfa increased from 285 MT in 1944-45

to over 1,542,650 MT in 1969-70. In early 1970, a

sudden decline in production occurred primarily

due to competition of foreign producers. Later, the

steady increase of energy cost and new air pollution standards decreased the profit margin in dehydrating. Many plants were closed and production fell below 1,181,818 MT.

Wet fractionation of freshly harvested crops can

reduce the energy requirement because the pressed

forage contains about 50 percent less water to be

evaporated per MT of final produce. The latent heat

from the dryers’ exhaust gases was recycled for use

in the evaporation processes, resulting in less air

pollution.

(TO WASTE)

The Valley Dehydrating Company (VDC), Sterling, Colo. (fig. 13) converted one of their existing

plants to Pro-Xan production. The Department of

Energy (DOE) supported the conversion as a means

of demonstrating the efficient energy conservation

possibilities in alfalfa dehydrators. With this funding, the research efforts of the USDA Western Regional Research Center, U.S. Department of Agriculture at Berkeley, Calif., could be realized in a

new LPC production plant in the United States. The

process equipment and operating parameters have

been described in several publications (23,24).

The results of a detailed study of this company

by Edwards, et al. (25), were published as a DOE

report. The exceptionally high level of technology

associated with this industry can be seen in table

11, which shows the considerable cost investment

for conversion of a conventional 18 MT/hr dehydration plant to a 36 MT/hr Pro-Xan plant. Because of

this high investment, it would be prohibitive to construct a similar factory in the humid tropics without

previous extensive studies of available plant material at the on-farm level,

During the experimental period, the plant operated at 13.6 to 21.8 MT/hr, and produced an average
Leaf Protein Extraction From Tropical Plants • 99

— —

Figure 13.—Aerial View of the Valley Dehydrating Co., Sterling, Colo.

LPC yield of 12.8 percent (dry basis). The VDC plant

consumed 25 percent less total energy. Based on

the experience at VDC, future LPC plants are projected to reduce overall energy consumption by 35

percent. The VDC products have been marketed

readily; the press cake has been sold to cattle

feeders at a price equivalent to dehydrated alfalfa,

and the LPC to a broiler producer at prices varying from $391 to $530/MT. Animal performance

trials using VDC produced products were highly

satisfactory. Projected current cost of a new LPC

plant processing 36 MT of chopped alfalfa per hour

is $4.7 million (table 12); the cost of converting an

existing 18 MT/hr dehydration plant to a 36 MT/hr

LPC plant is estimated at $3.6 million. The calculated rate of return on investment for the new plant

was 12.0, 26.2, and 40,4 percent for operating

seasons of 130, 180, and 230 days, respectively

(table 13).

The Vepex process was the first large-scale direct

production method for LPC. It was built as a separate industrial unit not associated with a dehydrating industry. Its primary purpose was to maximize

Photo credit: Courtesy of R. H. Edwards

production of plant protein both for the fodder industry and for human nutrition. The process can

also use raw material other than alfalfa.

Another essential feature is use of the deproteinized brown juice (33). Some of the nitrogen

compounds present in the green juice are not precipitated by heat treatment, The soluble N in the

deproteinized residual brown juice can amount to

30 to 40 percent of the total N content in the green

juice. This can be used as substrate for feed grade

yeast production.

A flow sheet of the Vepex process is shown in

figure 14. Vepex plants are located in Denmark and

Hungary. The plant in Tamasi in southwest Hungary is temporarily closed to make energy-saving

improvements,

In Britain, the BOCM-Silcock Co, studied the

preparation of dry leaf protein concentrates on a

pilot plant level with the aim of creating a system

to provide reasonably priced protein for feed in the

form of storable products. The dry matter and

pressed crop had to be at least 14 percent, a limit

set by the European Common Market (78). The flow
100 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

—

Table 11.— Basic Equipment Requirements for a Modified

Pro-Xan Plant Processing 36.3 Mg (40 t) of Fresh

Alfalfa Per Hour

j@ Item Specifications No. req’d Total Connected

power, kW (hp)

Forage harvester/chopper . ,

Truck

Truck

Truck scale

Feeder

Wet grinder

Screw press

Hydrasieve

Steam injector

Centrifuge

Drier, Pro-Xan with

recycle system

Pellet mill, Pro-Xan

Bucket elevator, Pro-Xan

Pellet cooler, Pro-Xan

Scalper screen, Pro-Xan

Inventory scale, Pro-Xan

Bucket elevator, Pro-Xan

bad-out bin, Pro-Xan

Waste heat evaporator,

(3 stage, 2 effect)

with cooling tower

Drier, press cake with

recycle system

Grinder, dried press cake

Bag filter, press cake

Pellet mill, press cake

Bucket ● levator, press cake

Pellet cooler, press cake

Scalper screen. press cake

Inventory scale, press cake

Pneumatic transfer system,

press cake

Load-out bin, press cake

Boiler, with economizer

Air compressor

Pumps 27

Conveyors , wet product

Tanks, with agitators

Well

Heat exchanger.

Waste water treament

self-propelled , 12 ft header

22 ton, tandem axle, 34 ft

bed , diesel powered.

3/4 ton pickup

60 ton

40 tons/hr

10 tons/hr

single screw, 20 tons/hr

6 ft wide

3 in. dia.

decanter type , 80 gal/rein.

triple pass, 6,000 lb H 2O/hr

1-1/2 torls/hr

1-1/2 tons/hr

1-1/2 tons/hr

1-1/2 tons/hr

1-1/2 tons/hr

1-1/2 tons/hr

1280 cubic feet

40,000 lb E20/hr

30,000 lb H2O; 185°F

9 tons/hr

9 tons/hr

9 tons/hr

9 tons/hr

9 tons/hr

9 tons/hr

9 tons/hr

9 tons/hr

3328 cubic feet

400 boiler horsepower

36 SCFM

various , to 200 gpm

various, to 40 tons/hr

various , to 10,000 gal.

250 gal/rein

600 sq . ft. , shell and tube

unspecified

4

4

2

1

1

4

1

2

2

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

4

1

1

6

12

6

1

1

. .

29.8 (40)

298.4 (400)

179.0 (240) — --

85.8 (115)

44.8 (60)

30.6 (41)

1.5 (2)

11.7 (15-3/4)

0.4 (1/2)

— --

1.5 (2)

— --

173.1 (232)

122.3 (164)

224.9 (301-1/2)

23.5 (31-1/2)

233.1 (312-1/2)

2.2 (3)

30.6 (41)

0.4 (1/2)

23.5 (31-1/2)

41.0 (55)

7.5 (lo)

31.7 (42-1/2)

55.6 (74-1/2)

3.4 (4-1/2)

14.9 (20)

37.3 (50)

Tot al 1708.5 (2290.25)

~/ Not applicable. .

~/ Does not inclued pumps in evaporator installation.

SOURCE: Edwards, et al. (25).
Leaf Protein From Tropical Plants ● 101

Table 12.—lnvestment Costs for a Revised Pro-Xan

Plant with a Capacity of 36.3 Mg (40 t) of

Chopped Alfalfa Per Hour

Ite m Investment Cost,

dollar s

Equipment, harvesting and haulin g 504,400 .

Equipment process plan t 2,793,349 ”

Building s 282,50 0

Lan d

3

46,80 0

Engineering and installation cos t

4

1,117,34 0

Tota l 4,744,389

1 Based on May 1982 prices.

2 Buildings include space for all operations except long term bul k

storage which is treated separately .

3 Six acres

4 Assumes 40 percent of cost of process plant equipmen t

SOURCE. Edwards, et al (25)

Table 13.—Annual Operating Costs, Revenues, and Return on lnvestment for the Revised Model Pro-Xan Plant

cos t (dollars) at season length (days )

Item 130 180 230

Annual Revenues

Dehydrated press cak e

Pro-Xan

Total Revenue s

Annual Costs

Alfalfa , raw material

Chemicals

Natural g a s

Electricit y

Fuel and oil

Maintenance and repairs

Labor

Administration

Property taxes

Insurance

Interest

Depreciation

Storage costs

Marketing costs

Transportation costs

Total cost s

Total earning s

Total Investment

Annual return on investment (%).

2,645,261

1,803,023

4,448,284

766,48 0

60,12 6

516,66 3

177,66 3

131,56 0

407,92 3

182,52 0

71,100

19,926

54,676

499,491

336,317

143,162

73,626

436,304

3,877,537

570,747

4,744,389

12. 0

3,662,669

2,496,494

6,159,163

1,061,280

83,251

715,377

245,995

182,160

451,923

252,720

71,100

19,926

54,676

537,027

336,317

198,225

101,944

604,113

4,916,034

1,243,12 9

4,744,38 9

26. 2

4,580,07 8

3,189,96 4

7,370,04 2

1,356,08 0

106,37 7

914,09 4

314,32 7

232,76 0

495,92 3

322,92 0

71,10 0

19,92 6

54,67 6

574,56 3

336,31 7

253,28 7

130,26 1

771,92 2

5,954,53 3

1,915,50 9

4,744,38 9

40. 4

1 plant capacity 36.3 ).& (40 tons) chopped alfalfa (22 percent dry utter) per hour .

SOURCE:Edwards, et al.(25)
102 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Figure 24.—Material Flow in Vepex Process

FLUE GAS

1

DRYER

84,0 Kg I

GREEN

PROTEIN GONG.

SOURCE: Koch (48).

sheet of this LP fractionation process

figure 15.

STEAM

is shown in

‘When the full-scale plant was built, it required a

growing area of 480 ha within an 8-km haulage radius. To operate at full capacity, the plant had anticipated producing lye-treated straw in the idle

season. However, the straw feed was not acceptable in Britain, and the new plant was shut down

after a brief interval of operation because the short

production period made it inefficient to operate

(79).

In New Zealand, Alex Harvey Industries, Ltd., in

cooperation with the Ministry of Agriculture and

Fisheries and the Broadlands Lucerne Company,

is planning to establish a plant to produce a leaf

protein concentrate with 47 to 50 percent crude

protein content and high levels of xanthophyll and

carotene pigments. This will be used for poultry

feeding, A high fiber pellet for ruminant stock will

also be produced. The plant will have a capacity

of 10 MT/hr of green alfalfa and be operated by

geothermal steam (67).

Two pilot plants managed by agricultural cooperatives began operation in Japan in 1981. Eac h

processes 2.7 MT/hr of fresh herbage. One of them

has facilities to separate LPC by centrifugation, condense green juice by reverse osmosis, condense

brown juice by heating, cultivate yeast using brown

juice, and make water from fibrous residue (58).

Preparation of Colorless Edible

Proteins From Alfalfa

The processing of LPC to obtain a food-grade

product was reviewed by Bray (12). Green LPC can

be produced economically. However, some problems exist in human acceptance of protein concentrate prepared by heat precipitation at 820 C: its

green color, grassy flavor, and low volubility,
Leaf Protein From Tropical Plants ● 103

Figure 15.—The BBOCM-Slicock Green Crop

Fractionation Process

SOURCE Thrlng (78)

A step in preparing improved protein in larger

quantities by solvent extraction has been reported.

Ineritei (38) found that freshly prepared coagulum

could be decolonized with an acetone and isopropanol mixture. The treatment improves flavor and

texture and gives a prolonged shelf life to the light

cream-colored product by removing the lipids. The

lipid distribution in green LPCs prepared from four

tropical plants was analyzed by Nagy, et al. (55).

The sale of lipid components, especially xanthophyll and B-carotene, and solvent recovery with

solar power in the tropics could decrease the cost

of this process.

Solvent extraction does little to improve the nutritional value of LPC. The tannin-damaged leaf protein concentrates are not or are only slightly improved nutritionally, Only a small amount of adsorbed tannins can be removed (Ii’).

In the heat fractionation process, after isolation

of the green protein at 55° C, in many plants two

additional white protein fractions can be separated:

one at 64° C and another at 820 C (77). The white

protein fraction prepared from alfalfa is nutritious,

with a protein efficiency ratio (PER) similar to that

of casein (9).

The heat coagulated proteins are practically insoluble. It was suggested that they could be used in

soups, gravies, cheese, and cookies (7). Food technologists for industrial application require certain

functional properties for proteins. If leaf proteins

could be processed to possess the desired properties, they would have wider use in the food

industry.

Since solvent extraction of undried green protein

has been costly and only partially effective and the

white protein prepared by heat precipitation is insoluble, radically different and more complex procedures for producing soluble white and blandtasting protein have been initiated.

In diafiltration, water is added to clarified alfalfa

juice during ultrafiltration so that small molecular

weight components can be washed through a membrane. On a laboratory scale, diafiltration, after a

mild heat treatment and centrifugation for clarification, resulted in a freeze-dried product that was

cream-colored and highly water soluble (46).

Pilot-scale ultrafilter units were tested by Knuckles, et al. (44) for concentrating and purifying soluble alfalfa leaf protein solutions after coagulating

the protein at 60” C. Operating temperature was

generally maintained at a low 100 C to avoid

microbial growth and precipitation of the heat

labile protein. The clarified alfalfa juice was concentrated to one-tenth of original volume, producing protein concentrates containing about 50 percent crude protein and 10 percent ash. Using diafiltration, water was added to the concentrated

alfalfa juice until the permeate volume was 10 times

the original sample volume. This method resulted

in material containing 70 to 76 percent protein,

Dried protein products were tan colored despite the

removal of more than 86 percent of the ortho dihy -

droxy phenolic compounds.

The ultrafiltration systems tested by Knuckles

and his coworkers cannot produce light creamcolored protein concentrates of greater than 90 percent purity. Because of their high cost and ineffectiveness, they are not viable methods for large-scale

purification of alfalfa protein.

Flocculants are used to remove suspended solids

from solution, Knuckles, et al. (47) reported their

work with 54 commercial flocculants tested to improve the separation of the green chloroplastic protein fraction from alfalfa juice. With a l-percent

level of cationic flocculent, the chloroplastic fraction was separated by continuous high-speed centrifugation. Residual sediment was less than 0.5

percent; however, the processing rate was low

(11.41/min). This technique also proved to be effective as pretreatment in membrane filtration. The
104 . plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

treated juice yielded greater soluble protein content

than the untreated control,

Knuckles and Kohler (43) prepared soluble leaf

protein concentrates (light tan colored). According

to the authors, these should be acceptable as a food

source. However, no cost data is given. Gel filtration was previously used for fractionation of LPC

by Fishman and Burdick (29) in characterization of

protein of Coastal Bermuda grass proteins. The use

of filter gels such as Sephadex is costly in even analytical processes. Freeze-drying is also a very expensive process because the special equipment is

expensive and requires high energy input. Special

proteins such as active enzymes may be prepared

by this method for biochemical or medicinal purposes. Comparing quality and price, the proteins

separated by gel filtration cannot compete with the

Fraction I protein of tobacco, which can be prepared by crystallization and is water soluble. Dr.

Wildman will discuss this unique protein in complete detail.

Environmental and Cultural Aspects

Nature and tradition have created richly variable

cultures in tropical areas. It is difficult to design

a general plan for a leaf protein extraction system

for the entire tropical zone. It is evident that the

whole system has to be geared to the natural and

cultural local environment: the climate, physical

location, soil fertility, and local cultural habits.

Two-product use is a key to the viability of the LPC

process. Ruminants must remain in the chain of

protein production to use the pressed residue. In

countries such as India, dairy animals or goats will

be used on a smaller scale operation than that involving beef cattle in developed countries. The

green LPC could be fed to humans or to calves as

a milk replacement, saving milk for human consumption. In Islamic lands, cattle, lambs, goats, and

rabbits could be fed the pressed residue, and

chickens and ducks the green concentrate. In Latin

America, the green juice could be fed to pigs and

chickens, and the pressed residue to beef or dairy

cattle.

The increasing protein shortage in the tropics

cannot be alleviated effectively by village scale production of LPC, especially if it is used only for infant feeding. At the First International Conference

on Leaf Protein Research held recently in Aurangabad, India, there were arguments regarding infant feeding trials between the representative of the

bilateral and multilateral donor agencies and the

recipient of grants for a children’s feeding trial on

one side and a highly respected local scientist on

the other. The scientist claimed that “There is no

doubt that leaf protein is good for protein and

carotene nutrition. But its use in children feeding

trials is considered unethical, purposeless, and unscientific. It is argued that the scope of the

pigmented leaf protein in food is limited to the individual family or to communities of no social and

economic disparities, Its production and use as a

means for overcoming the protein and carotene deficiency in human nutrition is not a practical proposition” (70).

Advocates of infant feeding claim that infants respond favorably to feeding formulas containing

alfalfa LPC. This claim could be contested. A protein-depleted infant would respond rapidly to any

proteinous feeding. The effect of prolonged infant

or child feeding of crude alfalfa green protein has

not been properly evaluated. The following facts

are disturbing. It is well documented that saponins

of alfalfa impede the growth of chicks (16). Its tannin-phenol complexes are not digestible; their interaction with digesting enzymes of infants can be

damaging, The biologically active coumestrol present in alfalfa was found in leaf protein concentrate

(45). In the growth of children, the possibility of ill

effects caused by the physiologically active ingredients of alfalfa green protein after prolonged feeding must be recognized. The dietetical value of the

touted laddu, a product of high sugar content, also

remains questionable. The large sum of research

money spent did not produce basic data on possible long-term undesirable effects of the use of alfalfa

LPC and did not reduce substantially the everincreasing number of ill-fed children,

LPC as an emergency food for humans, as was

suggested by Pirie for England during World War

II, should be considered, Experimentally, it has

proven to be nutritious; however, the author is

against human use of LPC, especially that of alfalfa,

because of incomplete testing and the possible

presence of antinutritional factors. The small-scale

production of LPC should not be rejected entirely.

In extreme poverty, it could be incorporated as a

protein source into native dishes. However, for

human consumption of LPC, plants should be selected from local green leafy vegetables such as collard, mustard green, and other brassicas.

Pirie (63) suggested at the Belo Horizonte

meeting in Brazil: “Except for infant feeding,

nothing could be gained by extracting protein from

leaves that can be eaten as green vegetables. The

best way to use LP to improve the nutrition of unweaned infants is to give it to the mother rather

than the infant, A broad-minded approach to bot-
Leaf Protein From Tropical Plants . 105

any is needed; the present occupation with alfalfa

is unfortunate. ”

Advocates for LPC feeding for children cite the

importance of carotenoids in diets of ill-fed children. LPC could supply these but carrots, tomatoes,

and green leafy vegetables could also supply children with the needed carotene.

It is obvious that a farm’s topography and size

will be decisive factors in determining its ability

to produce LPC. Small hamlets and subsistence

farms will not be able to participate in LPC production, On small farms in the mountainous areas of

the tropics, pods of winged beans and leafy vegetables such as collards, mustard greens, amaranthus, or even spinach could be additional sources

of proteins and carotenes to supplement the family’s daily consumption of beans and corn. Bananas

or plantains, cassava, or yams are staples in such

areas. It is difficult to believe that the wife of a

struggling farmer in the Tropics will harvest leaves,

pound them, filter the juice, and prepare a coagulum for food. Alternate sources of protein might be

more acceptable to the low-income farmer. For example, the breeding of rabbits could be popularized

on small farms. Harris, et al. (30), proved that dried

tropical leaves, even those of cassava which are unFigure 16.—Screw Press

fit for LPC production, supported the growth of rabbits and gave good results.

In a proper leaf protein preparation process, all

products must be effectively used and not wasted.

Since deproteinized juice cannot be used in small

village units for yeast production, it should be used

to irrigate fields. The fractionation process to white

proteins would be a prolonged procedure with

small yield for feeding trials. Similarly, the use of

complicated purifications by ultrafiltration and gel

filtration would be impractical.

The quality of life in rural areas of less developed

countries has to be raised; however, a single, small

industry like the bicycle-driven LPC production system used in India and involving a $3,000 investment will not substantially help alleviate the problems (fig. 16),

More moral and material support should be given

to the plan of Joshi (41), which is a healthy transition to the on-farm use system. He suggested that

in India LPC production could be incorporated into

a small, cooperative dairy farm to improve animal

husbandry for selected cows and to increase milk

production, This would be practical, Dairy cooperatives are being used successfully in Europe,

where the milk is collected for central processing

and distribution.

Operated by Human Power

in India

Photo credit: Courtesy of R. J. Joshi

24-503 0 - 83 - 8
106 • Plants: The potentials for Extracting Protein, Medicines, and Other Useful Chemicals— Workshop Proceedings

The on-farm use system has been studied only

with alfalfa and ryegrass. Using legumes, these

model experiments could be duplicated in tropical

countries, especially in Latin America where agricultural practices are well developed, land is available, and relatively simple technology could be successfully adapted to individual needs. The introduction of this type of system into areas of sugarcane

production would reduce the acreage given to that

crop, an economically sound decision, There is the

possibility of substituting leaf protein for high protein feeds, such as soybean meal, in poultry and hog

protein rations which are now imported into tropical areas.

As discussed in the on-farm use section, a production system of medium capacity is probably the

level that will have a tangible effect on the protein

resources within an area without disturbing its environment. There is no waste; the animal manure

can be returned to the fields to improve the soil,

and some of the pressed juice can be used for irrigation. The production facilities could process

plant material contracted from neighboring farmers. A higher income level would result from more

intense agriculture, which easily could be adapted

to the existing conventional system. This size of

agro-industry will not put a strain on electricity.

The processing machinery could use small tractors

as a source of power, It will not require a large

amount of water, and only simple tools are needed

for maintenance.

Research Needed

Leaf protein fractionation would increase the protein production of a given area universally. The

basic farm equipment has been designed and properly evaluated, and existing machinery can process any fresh green crop with proper N level and

extraction. The production level should be selected

according to the needs of an ecosystem and modified according to the traditions and religious bias

of the local population. Suitable plants should be

studied in more detail, possibly using a mediumscale experiment at the production site. However,

before expansion to the Pro-Xan type of operation

can be contemplated, it is imperative that longrange studies be made of potential plant material

at the on-farm use level.

USDA research centers and U.S. land-grant universities and tropical research centers in developed

countries should have sufficient funds for the remaining basic and applied research needed for LPC

extraction. An international cooperation between

U.S. institutions and host institutions funded by

AID should be developed for applying the research

results in countries in the Western Hemisphere that

would benefit from agricultural development based

on LP extraction. A parallel program should enable

scientists from host countries to learn the chemical

and physical methods of production and quality

control of raw material and finished products.

The host country scientists would offer the necessary data required for successful implementation.

The following salient points must be carefully investigated by local scientists before a system and

site are chosen:

1. Market research to determine need and acceptance of products

2. Availability of suitable land

3. Likelihood of undisturbed flow of plant

material for processing.

The next phase of investigation should be nutritional evaluation of LPC products with large and

small animals: cattle, milk cows, goats, rabbits, pigs,

and chickens, The preparation of proper feed mixes

should not be neglected. It is not sufficient to

prepare a nutritionally balanced feed mixture; it

should be readily acceptable by the animal and

should have good keeping qualities,

Farm-level processing machinery has been well

designed for disintegration and pressing. Only that

used for the separation of green protein concentrate

needs more investigation to obtain simpler and

more effective equipment. An inexpensive basket

centrifuge would probably be useful in this step of

the process,

Well organized on-farm use of LPC could provide

a thorough evaluation of tropical plants using medium-size technology and pave the way for the development of large-scale production of LPC—especially in tropical countries where advanced technology and sufficient amount of capital are available, such as Brazil, Puerto Rico, and Venezuela.

After evaluation of plant sources on a farm scale,

a commercial-size production facility is more likely to succeed.

While the capital requirements for large-scale

production are high, the return on investment is

also likely to be high because of the low labor costs

and year-round operating season. The effect of the

length of the operating season on return on investment is illustrated in table 13. The use of government subsidies to set up cooperative, commercialscale plants might help initiate the new industry

(26). Additional research funds should also be allocated to study low cost, more efficient extraction,

dewatering, separation, and evaporation tech-
Leaf Protein From Tropical Plants . 107

niques that are suitable for large-scale LPC production from tropical plants studied previously and

selected from intermediate-size studies.

Acknowledgment

The author is indebted to Professor Emeritus

Hjalmar D. Bruhn and Dr. Richard H, Edwards for

their guidance, data, pictures, and final reviewing

of the manuscript; Dr. Richard G. Koegel for a daylong conference at the University of Wisconsin on

the machinery of an onfarm use system; Dr. Walter

J. Bray for permitting the use of economic evaluation data of village level production of LPC in India, and N. W. Pirie for pictures of machinery developed at the Rothamsted Experimental Station,

Harpenden, England. Only with their prompt and

valuable assistance could I have written an up-todate report on the present status of LPC extraction

in the Tropics and project a positive, progressive

plan for its future.

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1980.

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24:1177, 1976.

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Value of Alfalfa Leaf Protein Concentrate (Pro-Xan)

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Four Tropical Leaves, ” J. Agric. Food Chern.

26:701-706, 1978.

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62. Pirie, N. W., :“ A Simple Unit for Extracting Leaf Protein in Bulk, ” Expl. Agric., 13:1 13-118, 1977.

63. Pirie, N. W., “Appropriate Leaf Protein Technology.”

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64. Pirie, N. W., “Some Controversial Aspects of Leaf

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66

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Heath-, S. B., ’’The Performance of the Machinery at

Present Available for the Expression of Juice From

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Wilkins (cd,], British Grassland Society and British

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71, Sotomayor-Rios, A., and L. Telek, “Forage Yield and

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81-1527, ASAE, St. Joseph, Mich., 1981.

74. Straub, R. [., Bruhn, H. D., and Barrington, G. P.,

“Plant Juice’ Protein Separation and Recovery,” ASAE

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75. Straub, R. J., Basken, K. E., Koegel, R. G., and Bruhn,

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77. Telek, L., “Preparation of Leaf Protein Concentrates

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78<

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Thring, J. M., “The BOCM-Silcock Green Crop Fractionation Process, “ in Green Crop Fractionation, R.

J. Wilkins (cd.), British Grassland Society and British

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Thring, J. M., “Closing of LPC Plant in Britain, ” personal communication, 1982.

80. Vartha, E. W., and Allison, R. M., “Use of Residue

from LPC Productionin Sheep Feeding,” Proceedings

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81. Vartha, E. W., Fletcher, L. R., and Allison, R. M., “Use

of Residue After Extraction From Lucerne and Tama

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82. Vosloh, C. J., Jr., Edwards, R. H., Enochian, R. V.,
110 Ž P/ants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Kuzmicky, D. D., and Kohler, G. O., “Leaf Protein

Concentrate (Pro-Xan) From Alfalfa: An Economic

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1976.

Selected Readings

Allison, R. M., “Leaf Protein as an Animal and Human

Foodstuff, ” Chemistry and Biochemistry of Herbage,

G. W. Butler and R. W. Bailey (eds.], ch, 29, vol. 3 (London and New York: Academic Press, 1973).

Kohler, G. 0,, Wildman, S. G., Jorgensen, N. A.,

Enochian, R. V., and Bray, W. J., “Leaf Protein in Relation to Forage Crop Production and Utilization” in Protein Sources and Technology: Status and Research

Needs, Milner, M,, Scrimshaw, N. S., and Wang, D.

I. C. (eds.) (Westport, Corm,: AVI Publishing Co,, 1978),

pp. 543-568.

Pirie, N. W., “Proteins,” in Modern Methods of Plant

Analysis, K. Paech and M. V. Tracey (eds.), Springer

Verlag, Berlin, Gottingen-Heidelberg, Germany, vol. 4,

1955, pp. 23-68.

Pirie, N. W., “Leaf Proteins, ” Ann. Rev. P1. Physiol. 10:33,

1959.

Pirie, N, W., “The Direction of Beneficial Nutritional

Changes, ” Ecol. Fd. Nutr. 1:279, 1972.

Pirie, N. W., Leaf Protein and Other Aspects of Fodder

Fractionation (Cambridge, England: Cambridge

Uni\rersity Press, 1978).

Telek, L., and Graham, D., Leaf Protein Concentrates

(Westport, Corm.: AVI Publishing Co., 1983).
MOLLUSCICIDAL AND OTHER ECONOMIC POTENTIALS OF ENDOD*

Aklilu Lemma

Senior Scientific Affairs Officer, United Nations Centre for Science

and Technology for Development, New York, N.Y. * *

Abstract

Ended is the Ethiopian name for Phytolacca

dodecandra, a full shrub closely related to the

American pokeweed, Phytolacca americana. The

young green leaves and shoots are edible protein

sources after they are boiled and the water is discarded. An extract of saponin from P. dodecandra

berries can be used as a molluscicide in the control of schistosomiasis and other snail-borne diseases. The berries have long been used as soap for

washing clothes, and roots and leaves, although

well-known for their toxicity, have been used as

medicine for various ailments and as abortifacients.

Recently, ended berries also have been discovered

to possess potent spermicidal properties useful for

birth control; aquatic insect larvicidal properties

potentially useful in the control of mosquitoes and

other water-breeding insects; trematodicidal properties for control of the larval stages of Schistosoma

and Fasciola parasites; hirudinicidal properties for

control of aquatic leeches; and fungicidal properties for the potential topical treatment of dermatophytes. Most of these studies are in experimental

stages and need further support.

Extensive studies of molluscicidal properties of

ended since 1964 suggest a new approach to the

control of schistosomiasis and other snail-borne diseases by using locally produced ended on a community self-help basis. Commercially available

chemical molluscicides are beyond the reach of developing countries because of their high cost, so ended or similar plant molluscicides that can be developed locally may be very valuable to poorer

countries affected by these diseases. Ended’s other

newly discovered properties might provide additional economic incentives to develop it.

Careful agronomic studies of ended over a 5-year

period led to the selection and experimental cultivation of 3 out of 65 strains collected from different

ecological zones in Ethiopia. The three strains selected had high molluscicidal potency (two to three

times more than previously used unselected

strains), produced large yields of berries, and were

highly resistant to insect pests. Application of new

tissue culture techniques at the Plant Products Institute in Salt Lake City, Utah, is providing methods

*The opinions expressed in this paper are those of the author and do

not necessarily reflect those of the United Nations.

* ● Formerly Director, Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.

of cloning and cultivation for mass propagation of

the plant. Ended is being used as a model plant by

a biotechnology development program investigating in vitro biosynthesis of an active principle

through a continuous calus-cell culture system. The

cloned ended plantlets from Utah and the seeds of

selected strains from Ethiopia are being grown experimentally in Ethiopia, Zambia, Swaziland, Brazil, and the Philippines.

The World Health Organization (WHO) Collaborative Centre for Traditional Medicine at the University of Illinois, Chicago, tested ended for mutagenic

properties to determine its safety for widespread

use. The results were negative, confirming an earlier study that ended has no mutagenic activity

under the different experimental conditions used.

Encouraged by these developments, an International Workshop on Ended was convened in Lusaka, Zambia, in March 1983. The workshop reviewed all studies on this plant, identified gaps in

knowledge, and developed specific projects that

could be undertaken as collaborative ventures by

a worldwide network of interested institutions and

individuals.

Description of the Plant

Ended is the Ethiopian name for the soapberry

plant Phytolacca dodecandra (L’ Herit) (Synonyms:

P. abyssinica Hoffin., Pircunia abyssinica Moq.), a

member of the Phytolaccaceae family (fig. 1). The

distribution of this plant is east, west, central, and

southern Africa and parts of South America and

Asia (l).

Ended has small berries which, when dried, powdered, and mixed in water yield a foaming detergent traditionally used in Ethiopia and elsewhere

for washing clothes. In Ethiopia, ended exists as

two main varieties, the more powerful arabe with

pink berries and ahiyo with grey berries.

The plant is a rapidly growing climber with hanging branches. The plant’s average height is 2z to 3

meters, although it can reach a height of up to 10

meters. Under favorable climatic conditions in

Ethiopia, the plant bears fruit twice a year, in

January and July.

Phytolacca dodecandra L’Herit and the closely

related Phytolacca americana L., commonly known

in the United States as pokeweed, long have been

recognized for their varied uses. Different parts of

the plant, including the leaves, fruit, and roots, are

111
112 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Figure 1 .—Phytolacca dodecandra (Ended plant)

widely regarded for their emetic, purgative, taeniafugal, abortifacient, detergent, antisyphilitic, and

other properties (2),

Discovery and Early Studios

In 1964, while doing an ecological study to determine the distribution of schistosome-transmitting

snails in a small stream in Adwa, northern Ethiopia, large numbers of dead snails were found in

areas immediately downstream of local people

using ended to do their laundry. Live snails were

abundant in areas further upstream and downstream from laundry sites. This led to subsequent

studies of the molluscicidal property of this plant

(3,4,5). The results obtained from these studies indicate that this or similar local plant products could

be used as molluscicides to control schistosomiasis

and other snail-borne diseases on a sustainable

community self-help basis.

About 10 to 20 parts per million (ppm) of the sundried, ground ended berries diluted in water kill

schistosome-host snails within hours of exposure.

Ended’s molluscicidal potency remains stable over

a wide range of water acidity/alkalinity (pH) and

with varying concentrations of organic and/or inorganic matter in the water, and is not significantly affected by solar ultraviolet light, In contrast,

copper sulphate, the well known and widely used

molluscicide, is adsorbed by organic and inorganic

matter in treated bodies of water; sodium pentachlorophenate, another important molluscicide, is

rapidly destroyed by ultraviolet light; and the widely used Shell product Frescon® is affected by the

pH of the water in which it is applied (4,6).

Since the discovery of the molluscicidal properties of ended in 1964, more than 40 scientific articles have been published and several patents registered on different aspects of the plant (7,8,9). Unfortunately, because most of these publications are

in journals with relatively limited distribution, such

as the Ethiopian Medical Journal, the research

results have not been accessible to many scientists

and potential users in different parts of the world

(5).*

Role Of Molluscicides

The role molluscicides can play in effective control of schistosomiasis and other snail-borne diseases of humans and livestock has been well established. Numerous schistosomiasis control projects

in Egypt, the Sudan, the Middle East, Japan, the

Philippines, China, Brazil, and other countries have

shown that snail control by molluscicides, either

alone or in combination with other methods (e.g.,

chemotherapy, environmental measures, health education, etc.), can rapidly reduce or eliminate disease transmission. In recent years, there has been

a marked change in snail control strategy from

“blanket” or areawide treatment to seasonal and

site-specific treatment. For more efficient, economical, and long-range results, focal mollusciciding efforts should be coupled with selected population

*To make this information available in a single source, we have compiled the widely scattered reprints and publications on this plant and

published them in a 522-page book along with a review of the status of

ended research as of the publication date. Copies can be obtained free

of charge from the authors (Aklilu Lemma, 145 Broadview Ave., New

Rochelle, N.Y. 10804; or Dr. Donald Heyneman, Department of

Epidemiology and International Health, University of California, San

Francisco, Calif. 94143).
Molluscicidal and Other Economic Potentials of Ended • 113

chemotherapy and appropriate health education

and community involvement. Such an integrated

control strategy will continue to be the most effective approach until an appropriate vaccine against

this disease is developed.

Comparison with Other Molluscicides

Several chemical molluscicides have been used

for control of schistosomiasis and other snail-borne

diseases over the last few decades. Among the most

notable are copper sulphate and other copper salts

which in the past have played major roles but largely have been discarded because of low efficiency

and inactivation by various organic and inorganic

matter in water. Another popular chemical molluscicide was sodiumpentachlorophenate, also discarded because of its irritant effect on human skin

and rapid decomposition by solar ultraviolet light.

The shell chemical product Frescon® (Ntritylmorpholine), known to be highly sensitive to

variations in water pH, and the Japanese product

Yurimin are no longer produced. The Bayer Co.

product Bayluscide (niclosamide) is the best molluscicide commercially available and the only

one recommended by WHO for widespread use.

Because of the high cost of this product (more than

$25,000 per metric ton (MT) in 1981), only a few

developing countries are using it and on a limited

scale with external financial assistance. The lack

of market for molluscicides discourages private enterprise from searching and developing other products, including the organo-tin compounds, which

have some promise for slow release application.

Plant MoIluscicides

In recent years, as a consequence of the constraints to chemical molluscicidal use and of the

encouraging results obtained from ended in Ethiopia, interest in plants with molluscicidal properties has increased. Thousands of plants have been

screened for molluscicidal activities using a standard WHO procedure. The comparative potencies

of ended and some of the leading chemical and

plant molluscicides are shown in tables 1, 2, and 3.

Many plant molluscicides, such as from the fruits

of Sapindus saponaria, Swartzia madagascariensis,

Balonites aegyptica, and the bark of Entad a

phaseoloides, contain saponins. The roots of Derris elliptica, the pulp of Agava susakaba, and the

leaves of Schima argenta have been reported in the

literature to have molluscicidal properties. All of

these are suspected to be harmful to the environment; there is long-established knowledge that they

are potent fish poisons. Ended is the most exhaustively studied of the known plant molluscicides and

provides a model for similar studies. Croton tiglium, C. macrostachys, Jatropha curcas, and Ambrosia maritima also deserve special consideration

(10,11).

The seeds of two species of croton, Croton tiglium and C. macrostachys, that grow abundantly in

the Philippines, India, and the Sudan, have high

molluscicidal potencies, For an unknown reason,

croton seeds are more active against Bulinus species of snails (transmitter of urinary schistosomiasis) than against Biomphalaria species (transmitter

of intestinal schistosomiasis). A more serious drawback of croton is that it is carcinogenic and highly

toxic to humans (12,13).

The seeds of Jatropha curcas, a plant that grows

abundantly in the Philippines and produces seeds

almost year-round, have a relatively high toxicity

against Oncomelania snails and more moderate toxicity against Bulinus species (14,15). WHO is sponsoring studies to identify the active ingredient and

determine the product’s stability under various

physical-chemical conditions and may undertake

further field trials in the Philippines, The seeds and

all other parts of the Japtropha plant showed no effect against Lymnaea snails, which transmit the

economically important major animal disease, facioliasis (16). Lymnaea snails are major agricultural

pests that multiply rapidly in rice paddies and destroy blue-green algae that are essential for nitrogen

fixation (47). In an attempt to control these snails,

scientists at the International Rice Research Institute in Los Banes, the Philippines, are introducing

and testing ended, which is very potent against

Lymnaea’s adult and oval stages.

The leaves and flowering tops of the Egyptian

plant, Ambrosia maritima (locally called damsissa),

have some molluscicidal properties that have been

studied for a long time. An infusion of the leaves

at a concentration of 1,000 ppm kills planorbid

snails in 24 hours (17); ended kills the same snails

at less than 10 ppm in 24 hours, A positive feature

of damsissa is that it seems to grow easily and reach

maximum growth at the peak of schistosomiasis

transmission in Egypt (11).

Nonovicidal Nature of Ended

While some of the chemical molluscicides such

as Bayluscide (niclosamide) are known to penetrate

egg masses and kill unhatched snails, others such

as Ended and Frescon® (N-tritylmorpholine) are
114 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

●

o
Molluscicidal and Other Economic Potentials of Ended Ž 115

Table 2.—Effects of Various Molluscicides on the Egg

and Different Sizes of Bromphalaria globrata

Expressed as 24-Hour LC90 (ppm.)a

small Large

Molluscicide s Egg s (l-3 mm. diam.) (10-15 mm. diamm. )

**

Ended 100.00 4.70 3.00

Bayluscid e 0.20 0.20 0.26

Fresco n 40.00 0.20 0.21

Copper sulphate 4.00 0.70 0050

Pentacloropheno l 1•0 0 0.65 1.00

aAdOpted from Lemma and Yau (20)

bEndod is active against Ly~~aea eggs at concentrations of 3-5 ppm in 24 hours

See text for possible explanation

Table 3.—Molluscicidal Potency of Butanol Extract

of Ended Against Various Species of Snailsa

Snail Species

(adults) 24-hr. L~ (ppm.) Investigators

— . —.- . . 

Biomphalaria glabrata (NIH) 3.0 ± 0.25 Lemma et al., 1972

Biomphalaria glabrata (Brazil) 2.3 ± 0.25 Paulini, 1971

Biomphalaria alexandrine (Egypt) 3.0 ± 0.25 Heynemann

and Limm, )971

Lemma et al., 1972

Biomphalaria pfeifferi (Ethiopia) 2.8 ± 0.25 Yohannes et al., 1970

Bulinus truncatus (Egypt) 3.4 ± 0.25 Lemma et d., 1972

Bulinus truncatus (Ethiopia) 1.4 ± 0.25 Yohannes et al., 1970

Lymnaea natalensis (Ethiopia) 2.8 ± 0.25 Yohannes et al., 197 0

Oncomelania nosophora (Japan) 1.6 ± 0.25 Wagner, 1971

Yasuraoka, 1971

aAdopted from Lemma and Yau (20)
116 ● Plants: The potentials for Extracting protein, Medicines, and Other Useful Chemicals_Workshop Proceedings

known to be nonovicidal at molluscicidal concentrations. This has often been cited as a disadvantage of ended (table 2). This was particularly valid

in the earlier days when “blanket” treatment or

areawide application of molluscicides was the recommended procedure for controlling snails. Under

those conditions, unless the molluscicide had

ovicidal properties, repeated applications were

necessary to kill the young snails hatched from

unaffected eggs.

However, recent field studies in Egypt, the Sudan, Brazil, and St. Lucia indicate that the ovicidal

property of a molluscicide may not provide the advantage attributed to it earlier. Repeated mollusciciding of such water bodies is necessary because

treated areas are rapidly repopulated by snails from

untreated parts of rivers or irrigation canals, even

areas treated with the highly ovicidal Bayluscide.

Under these circumstances, the ovicidal property,

or the lack of it, may not be a significant advantage

because the molluscicide has to be applied repeatedly on a regular basis,

In an attempt to determine whether ended was

nonovicidal to only certain species of snails, eggs

of different species of Biomphalaria, Bulinus, and

Lymnaea snails were tested at the Harvard School

of Public Health. Whereas 100 ppm or more were

needed to kill Biomphalaria and Bulinus eggs in 24

hours of exposure, 3 to 5 ppm killed all Lymnaea

eggs. These findings were further substantiated in

field trials with ended in Puerto Rico where Lymnaea, Marisa, and Physa eggs and adult snails were

destroyed by a concentration of about 5 ppm in 24

hours (5).

WHO Workshop on Plant Molluscicides

In response to the growing interest in molluscicides of plant origin, the scientific working group

of schistosomiasis of the UNDP/World Bank/WHO

special program of research and training on tropical diseases convened a workshop on plant molluscicides in Geneva, Switzerland, from January 31 to

February 2, 1983. The workshop evaluated and recommended some specific actions for developing

plant molluscicides. It recognized Phytolacca

dodecandra (ended) as the most promising plant

molluscicide studied to date. Subsequently, an international scientific workshop on ended was convened in Lusaka, Zambia, in March 1983. This

workshop reviewed all past and present work on

ended and recommended future areas for collaborative work among developing countries and among

developing and developed countries.

In a 5-year schistosomiasis pilot control study

with ended in Adwa, Ethiopia, the prevalence of

S. mansoni in children between the ages of 1 to 6

was reduced from 50 percent at the start of the project (1969) to 7 percent after continuous control for

5 years (1973). The incidence of disease throughout

the population in Adwa (17,000) dropped from 63

to 34 percent in 5 years. This included many incurable chronic cases in older individuals. This was

achieved by systematic application of crude ground

ended berries collected from the immediate neighborhood of Adwa (21).

Annual disease surveys during the study showed

a progressive reduction both in prevalence and new

reports of the disease in Adwa, while these figures

remained almost constant in the untreated nearby

village of Inticho, suggesting that the action primarily was due to ended applications reducing the snail

population (figs. 2 and 3). Ecological observations

Figure 2.— Prevalence Rates of Schistosoma mansoni

in Adwa Before and After Control Measures

by Application of Ended

I

●

AGE GROUPS

SOURCE: Adapted from Lemma, et al. (21).
Molluscicidal and Other Economic Potentials of Ended • 117

Figure 3.— Prevalence of Schistosoma mansomi in

Children 1-6 Years Old in Adwa and in the Control

Area of Intitcho

● — Adw a

o — Intitcho

5

69 70 71 72 73 74 75 76 77

YEAR

SOURCE’ Adapted from Lemma, et al. (21).

during these 5 years indicated that ended had no

obvious adverse effects on the microflora and fauna

of treated streams (21).

Significance of Application

of Schistosomiasis Control

Schistosomiasis is one of the most important and

rapidly spreading parasitic diseases of mankind, a

growing threat to large-scale irrigated agriculture

and hydroelectric power development schemes in

many tropical and subtropical parts of Africa, the

Middle East, the Far East, and many parts of South

America. An estimated 200 million to 300 million

people are affected by this debilitating disease, and

another 300 million to 400 million potentially are

exposed to it.

The spread of schistosomiasis is a tragic example of man’s actions. Well intended irrigation and

other water-related development projects in tropical countries often have created new breeding habitats for the snails that transmit this disease. Infected and noninfected people working in such

areas often must drink from, bathe in, and labor in

the same canals. Human wastes often are excreted,

dumped, or washed into the same water, leading

to the rapid spread of this disease, especially among

highly vulnerable children.

Inasmuch as schistosomiasis is a social disease,

its control poses a major social challenge. There

seems to be no single method to control schistosomiasis effectively. Ideally, effective control should

involve the combined uses of mass treatment of all

infected people, snail control using molluscicides

to interrupt disease transmission, health education,

and improved standard of living.

In spite of recent promising developments, there

still is no safe, effective, and affordable drug

suitable for mass treatment. Treatment by drugs

(containing toxic compounds) sometimes was more

tortuous than the disease itself. An excellent new

drug, Praziquantel, still is too expensive for mass

use. However, even if an ideal drug were available

and cured an individual, he or she probably would

be reinfected as long as the source of infection remained uncontrolled. Unfortunately, health education and improved environmental sanitation are

long-range measures, closely interwoven with

general socioeconomic and educational structures

of a community. They must rely on governmental

policies, plans, and available resources to increase

the standard of living of the affected population.

Under present circumstances, the most effective

and practical method of controlling schistosomiasis

is through a combination of selective treatment of

infected individuals and control of new transmission by killing the host snails at each proven site

of infection.

Community Participation

One essential component of the Adwa project

was active community participation. The provincial governor-general, the mayor of Adwa, and the

Municipal Council all were involved throughout

the duration of the program. Their roles in planning and executing the project were essential for

its ultimate success. The budget for the 5-year pilotcontrol project was provided by the Adwa Municipal Council. The Council also provided necessary

facilities and manpower, including a headquarters

for the project and local staff to run the field work,

collect ended from wild plants, or purchase ended

from local markets where it is sold as soap (21).
118 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Another major reason for community participation is to have the community, through its Municipal Council, continue the control program on completion of the 5-year experimental work. Involvement of the affected population in the control of

the disease on a “community self-help” basis is

critical to the long-term success of a program. Projects are all too often discontinued as soon as the

outside team leaves.

Detergent and Foaming Properties

The detergent and foaming properties of ended

have been tested (Shell Crane, pers. comm.) with

a detergiometer and compared with other commercially available detergents in a preliminary trial at

the Stanford Research Institute (SRI) in 1971. It was

found to be an effective clothes cleaning agent. Further studies should find ways to make the extract

serve as a supplement or substitute for other detergents. Ended has the advantages over some chemical detergents of being harmless to delicate fabrics

(such as fine cotton, linen, and wool) and of leaving the clothes noncompressed. Further, it is biodegradable and its use has no apparent deleterious

environmental effects. Experimental evidence suggests this as does its centuries of use in streams,

but more research should be done in this area.

The high foaming property of ended could be

modified for use in lightweight concrete and foam

rubber. It may also be possible to use it as a dispersant in perfume manufacture. Limited preliminary

studies indicate commercial potential, but a great

deal more investment and study is needed.

Larvicidal Properties

Studies at Harvard University on the comparative

toxicity of ended and other compounds on stream

flora and fauna showed that mosquito larvae are

particularly susceptible to the lethal effect of ended

(22). This led to other investigations which demonstrated the susceptibility of larvae of the notorious

black fly (Simulium spp.), which transmits river

blindness, or onchocerciasis, and larvae of the domestic house fly, Musca domestica (23,24). Further

development of ended as an insecticide for village

use could have public health significance. Since

snail and malaria-transmitting mosquitoes may

breed in the same type of environment, control of

snails with ended may have the added benefit of

reducing mosquito populations.

Hirudinicidal Property

The aquatic leech, Lymnatis nilotica, a major animal pest of livestock in many tropical countries,

is susceptible to ended (5). Ended has been used

for centuries in Ethiopia to control this pest. This

use should be improved for more effective protection of domestic animals against this debilitating

ectoparasite.

Trematodicidal Property

Schistosome cercariae and other trematode larvae are highly susceptible to ended. Infected waters

can be rendered safe for several days by application of small quantities of ended. The active ingredient can also be prepared in ointment form for application on exposed skin of workers in irrigation

canals as a prophylaxis against cercarial penetration. This has been tried at SRI with some success

using the tails of test mice coated with ended ointment and immersed in cercaria-containing water

(20).

Spermicidal Properties

Systematic biological screening of the butanol extract of ended showed it to be an extremely active

biological agent against human sperm, thus suggesting its possible use as a locally produced, vaginal foam birth control agent (9). Ended long has

been known and is widely used as an abortifacient

in traditional societies in Ethiopia and other parts

of East Africa. Recent laboratory studies have

shown it to cause strong uterine contractions (25).

Intrauterine injection of small quantities of ended

extract in pregnant mice causes sterile and apparently harmless abortion. In addition to preventing

pregnancy, it maybe useful as a “day after” pill (26),

Other Snail-Killing Properties

Ended is also effective against snails that transmit

other important human and animal diseases besides

schistosomiasis. Laboratory and field studies have

indicated that Lymnaea spp. are extremely susceptible to ended. These are the snail hosts of important cattle and sheep liver fluke that cause fascioliasis. Spraying pastures with relatively low concentrations of ended will kill snails, eggs, and infective larvae of the parasites without affecting the

animals or vegetation on which it is sprayed. In
Molluscicidal and Other Economic Potentials of Ended ● 119

view of the worldwide distribution of fascioliasis,

development of ended to control this disease could

benefit not only developing but also developed

countries.

Lymnaea snails, which multiply rapidly, reach a

biomass of 1.5 MT/ha in some ricefields in the Philippines and graze heavily on blue-green algae that

are carefully introduced and grown for nitrogen fixation in paddy fields (47), The International Rice

Research Institute in Los Banes, the Philippines,

is investigating the possibility of using ended to

control these snails (P.A. Roger, pers, comm.).

Fungicidal Properties

Biological screening tests have revealed that endod has a selective toxicity to dermatophytes, the

fungi that cause a variety of skin conditions, such

as athlete’s foot and ringworm, The possible use of

ended for treatment of these diseases needs further

investigation (27,45),

Toxicological Studies

One of the most important criterion for

widespread use of any molluscicide is its safety to

humans, animals using the treated bodies of water,

and local flora and fauna. The possibility of longterm negative effects from using such compounds

should also be determined. Preliminary studies on

the toxicity of ended to a variety of animal and

plant species and tests for carcinogenic properties

have been undertaken (4,28). Some of these earlier

tests have been recently reconfirmed at a WHO

reference laboratory at the University of Illinois in

Chicago (Norman Farnsworth, pers. comm.).

A comparative toxicity study in sheep and dogs,

as representatives of large ruminant and monogastric animals, both domestic and wild, that might

drink endod-treated water, has also been undertaken. Sheep force-fed with the water extract at a

dose of 1 gm/kg body weight died within 96 hours,

whereas a dose of 200 mg/kg body weight had no

apparent effect on kidney and liver function tests

done over a period of 4 days (29). Oral administration to dogs at a dose of about 100 to 200 mg/kg

body weight caused vomiting within minutes. Intravenous injection at the dose of about 50 mg/kg

body weight was lethal in less than 24 hours, but

8 mg/ml of blood did not show any significant

changes (29). Thus, although ended is known to be

hemolytic to red blood cells if injected intravenously, it generally is well tolerated by animals if administered orally. When taken orally by humans

and monkeys, it immediately causes vomiting so

most of the product fails to reach the intestine. The

emetic property of the berries is so strong that SRI

chemists considered using it to prevent possible

overdose from potentially dangerous drugs such as

sleeping pills. *

Continuous application of high concentrations of

ended solution to economically important plants

over long periods of time appears to act as a fertilizer, promoting more rapid growth of test plants

compared with controls given only water (4).

As with other molluscicides (20,30), small fish

and tadpoles are affected by ended at molluscicidal

concentrations. However, edible fish rarely breed

in the small streams and canals where disease

snails normally breed; adult frogs instinctively

jump out of treated waters; and large fish swim rapidly from endod-treated sites to avoid its irritant effects. Hence, the product does not appear to have

a significant impact on these animal populations.

Birds known to feed on berries of wild plants seem

unaffected, as do waterbugs in treated streams,

During the 5-year experimental period in Adwa,

treated streams were monitored for possible toxicity of ended to representative species of the flora

and fauna, and no apparent effects on the aquatic

ecology were noted. There has been no apparent

negative impact from ended use in rural communities where ended has been and still is being used

for washing clothes.

Our studies have shown that the active principle

in ended biodegrades rapidly. The lethal effects

following ended application to streams, canals, or

lakeshore persist for 24 to 48 hours, after which

time ended’s potency rapidly declines.

Ended berries have been used for washing

clothes in streams and lakeshores in Ethiopia and

other parts of Africa for centuries, with no apparent

toxic effect. Also, in Ethiopia and elsewhere in Africa, high concentrations of the ended leaves, roots,

or berries are taken orally for various medicinal

purposes, such as for purging intestinal parasites

and for abortion (2,25). If ended had any harmful

effects, surely it would not have survived centuries

of human use. As with all natural products used

by local people, its dangers would have been recognized and the substance discarded,

These assumptions were in part tested through

mutagenic studies done on Phytolacca dodecandra

*Since the active component in ended is a relatively large molecule,

it is assumed that it may not be able to easily penetrate the walls of the

gut and enter the bloodstream where it could cause much damage. Also,

itsemetic properties in regurgitating animals may give it a built-in protective mechanism to safeguard against its possible harmful effects.
120 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

by Lemma and Aimes (1974) on in vitro assays

using a Sahnonella typhimurium strain that since

has given possible false results in the presence of

histidine, a material normally found in most plant

extracts including ended. Since traces of histidine

from ended could have interfered in those tests, the

negative data obtained in the 1974 study were considered equivocal and new tests were undertaken

by Dr. N. R. Farnsworth of the WHO Collaborating

Centre for Traditional Medicine and College of

Pharmacy, University of Illinois, Chicago, using

strains of Salmonella that are not affected by

histidine. The results were all negative, confirming that neither ended nor pokeweed, which was

tested for comparison, have any mutagenic properties under the experimental conditions employed

(Farnsworth, 1983, pers. comm.).

However, conclusive evidence of mutagenic tests

and other chronic toxicity of ended or any other

similar product should come from carefully designed long-range toxicity studies in different species of animals, rather than from tests in isolated

in vitro cell systems. To this end, the author hopes

that WHO and/or another concerned organization

will finance such a long-range study on ended so

that its widespread use in areas where it is most

needed could be further promoted and effectively

applied.

Chemical Studies

The ended plant provides material of special interest to organic chemists involved in saponin

chemistry, partly because of the high percentage

by weight of crude saponins in dried berries, and

partly because of the chemical complexity of the

materials. Most chemical work on ended until now

has concentrated on the saponins of dried berries.

Although this work has yielded interesting chemical findings and valuable biological discoveries, according to Parkhurst, it seems that this is only “the

tip of the iceberg” in developing the chemical potential of ended (31).

Chromatographic separation of crude saponins

in ended demonstrates the dozens of compounds

present, of which only a few have been characterized. The nonsaponin fraction, amounting to 75

percent of the total weight of the dried berries, may

be broken down into petroleum-soluble lipids, water-soluble sugars, starches, pectins and gums, and

a water-insoluble fraction. Little is known about the

chemistry or potential uses of these fractions.

Abundant as the berries are, they represent a small

fraction of the plant, the rest of which is ample

material for future chemical study (35,36,37),

Valuable byproducts have been obtained through

the development and refining of endod. The watersoluble fraction with sugars and various polysaccharides, produced in the isolation of crude ended

saponins, remains to be studied. New pectins,

starches, thickening agents, material for fermentation to alcohols, and sources of rare sugars with industrial importance all may be found in the plant

material left after the berries are cropped. The

water-insoluble fraction, also not yet investigated,

may be useful as animal feed, a fuel, or a soil additive.

A green lipid material is obtained from the petroleum extraction of ended. While most of this

material is composed of palmitic, oleic, and stearic

acids, 12,5 percent consists of a nonsaponifiable,

bright orange, waxy material containing squalene

and a complex mixture of high molecular weight

alcohols—i.e., phytosterols and/or triterpenols. As

the value of ended saponins is established and production rises, large-scale development and additional uses for the saponin will follow and more

byproducts should become available.

Chemical studies to isolate and identify the active principle in the ended berries have led to the

discovery of a new compound, oleonolic acid glucoside, which Parkhurst, et al., have named Lemmatoxin (32,33,34) (fig. 4). Three different procedures have been developed in different laboratories

to extract the active ingredient from ended berries.

The first method, developed and patented by the

Tropical Products Institute in London in 1971, was

relatively complicated, based on methanol extraction followed by potassium hydroxide hydrolysis

in two steps (7). In 1972, a simplified method involving single-step butanol extraction from an aqueous suspension of dried berries was developed and

patented by SRI investigators in California (8,38).

Both of these procedures give extracts effective at

2 to 4 ppm, However, both procedures have the disadvantage of depending on importing extraction

solvents, thus demanding hard currency. This

shortcoming was finally overcome by the third and

perhaps most practical and promising extraction

procedure which is based on fermentation techniques. It was discovered by the Ethiopian chemist

Tesfaye Lemma, working under the author’s supervision at the Institute of Pathobiology in Addis

Ababa.

Improved Extraction Procedures

Water extracts of powdered ended berries after

defatting with benzene were more active in killing

snails than were extracts obtained without a defat-
Molluscicidal and Other Economic Potentials of Ended Ž 121

Figure 4.— Lemmatoxin-A

o 0

OH

SOURCE Parkhurst, et al (32)

ting procedure. The concentration needed to obtain

a 100 percent kill in 24 hours was 2 ppm. The increase in molluscicidal activity was proportional

to the degree of defatting. The molluscicidal potency of a suspension of ended left to ferment over a

period of time increased gradually for a long time

(up to 5 months) if the ended concentrations were

10 to 20 percent. On the other hand, if the concentrations were 0.1 to 1.0 percent, the molluscicidal

activity decreased within a few weeks. The best results were obtained when fermentation took place

at 22° C (39),

The fermentation-based extraction procedure

depends on practical, simple techniques using yeast

cells that are part of the normal flora of the berries.

When ground ended berries are soaked in water

and left in a warm place, they ferment rapidly and

eventually separate into a clear supernatant fluid

containing the active principle, and a residue,

mainly yeast cells and debris, The supernatant is

easily separated from the residue and can be dehydrated with small, locally constructed solar drying

chambers and ground into a fine powder. The powder then can be dusted directly over the infected

water or prepared in different formulations such

as flakes that can either sink or float on water

depending on the specific snail targets; made into

emulsion concentrates for spraying; or compressed

into special briquettes of different hardness for

slow release in water. In the case of briquettes,

farmers and villagers could easily be taught how

to prepare them, how much and how often (per

week or per month) they should be applied, and at

which specifically predetermined spots (based on

the volume of water to be treated and the degree

of hardness of the briquette) (5).

The simple fermentation chambers required and

the drying and processing apparatus for this molluscicide could be constructed by students at neighborhood schools, a local blacksmith, or itinerant

“barefoot technologists.” The apparatus must be

simple enough for easy operation by village-based

community-health workers. Although preliminary

studies to develop these possibilities have much

promise, the packaging of technology and knowhow have yet to be developed and standardized.

Yeast cells from the fermentation process can be

washed, sundried, and used as high-protein supplements for animal feed, particularly as additives for

chicken feed, These prospects, however, have not

yet been fully studied.

Another useful tool to be developed is a simple

procedure for calorimetric determination of the

concentration of the active principle of ended in

treated bodies of water. Such a device would allow

more effective use of the product in the field (40).

Agronomic Studies

While research on the toxicity, chemistry, extraction, and application of ended has been progressing rapidly since the discovery of its molluscicidal

properties in 1964, in general, studies on the agronomic aspects have lagged behind this research.

Detailed investigations of the agronomic aspects of

ended production were begun by Dr. Legesse W.

Yohannes and his colleagues only in 1972. These

efforts subsequently were enhanced by Dr. Charles

B. Lugt, a Dutch agronomic chemist, sent to work

in Ethiopia under a special grant from the Netherlands Government. A major goal of these studies

is to select and breed plants for favorable growing

characteristics, productivity, and high potency of

berries, Ended is a dioecious plant but can be propagated readily from berries and cuttings, Some

agrobotanical data on plant ecology, nutrition,

germination, spacing, and irrigation have been

gathered during the past few years, and studies on

the ecology of the plant and its pests have been

undertaken in Ethiopia (44).

The great climatic and ecological diversity of

Ethiopia apparently has given rise to several

geographic strains of Phytolacca dodecandra with
122 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

varying growth characteristics, yields, insect resistance, and molluscicidal potencies. In a 5-year

(1976-81] extensive agronomic study done on endod by Lugt, 65 different strains and varieties of

the ended plant collected from different parts of

Ethiopia were studied under comparable conditions. Three strains were selected for their exceptional growth characteristics, high molluscicidal

potency (two to three times more potent than the

originally used varieties), high annual yield (about

1,320 kg/ha), and high resistance to attacks by insect pests and drought conditions. The results of

these studies have been published in a book by Lugt

(41). The studies in Ethiopia also discovered that

the green unripe ended berries contain more active molluscicidal components than the ripe pink

berries, thus reducing time before harvest and damage done to ripe berries by birds (42,43).

One major difficulty with mass cultivation of endod is attack by larvae of a Gitoma drosophilid fly

which bores through the stem, selectively killing

young shoots of the plant (41,43). Although these

insects can be controlled effectively by the application of appropriate insecticides, agronomic studies

to select plant varieties with particular resistance

to this insect have been promising.

In a current study, Dr. Hugh Bollinger of Plant

Resources Institute, Salt Lake City, Utah, is undertaking ended tissue culture using the three selected

strains of ended supplied from Ethiopia by Dr.

Lugt. He is making significant advances on two

fronts:

1. Development of tissue culture methods of mass

propagation of selected vigorous strains of the plant

through cloning. Plantlets developed through Dr.

Bollinger’s cloning method are being supplied to

Ethiopia, Zambia, Brazil, and Swaziland for field

evaluation. The new procedure should improve significantly the prospects for mass cultivation of

known strains for large-scale field use.

2. Development of tissue culture system for in

vitro biosynthesis of Lemmatoxin, the active principle responsible for killing snails. This exciting approach uses “calus” cultures with proven high

molluscicidal potencies, Dr. Bollinger plans to expand these studies to produce the molIuscicide and

facilitate studies on nutritional and other biological

characteristics of the plant.

Cost Effectiveness of Endod

Questions about the economy and cost effectiveness of ended should be investigated. During early

stages of the study, it appeared that ended would

be more costly than other molluscicides. However,

two sets of questions must be asked before an adequate comparison of molluscicides to be employed

in Third World countries can be made:

1. Does the molluscicide have to be imported

from abroad? At what cost? For how long? Rapidly rising rates of inflation and the large quantities

of molluscicide required on a continuous basis are

key considerations. Can developing countries that

are debilitated by schistosomiasis but have limited

foreign exchange capabilities afford imported

molluscicides?

2. Can the molluscicide be produced locally in

sufficient quantities for large-scale use? If so, the

initial cost of production during the experimental

period presumably would be high, but what would

be future large-scale production possibilities? At

what cost? With what savings in hard currency and

buildup of local agricultural and production facilities? The possibilities and cost of introducing modern agricultural techniques, better yielding plant

varieties, and more insect resistant varieties should

be included in this evaluation.

It seems that since local production and processing of a multiple use plant product for internal consumption and foreign sale is preferable to continued depletion of limited hard currency, the initial

developmental costs should be considered as a high

priority investment. As improved methods of cultivation and improved plants are introduced, costs

should fall and both the usefulness and profit from

the products should rise. As nonmolluscicide uses

of ended, such as soaps, drugs, insecticides, and

foaming agents, are developed, its cost effectiveness

will increase proportionately.

The 1969-73 Adwa schistosomiasis control program that reduced disease transmission by about

85 percent used ended berries collected from wild

plants or bought from local markets. The cost was

Eth. $0.25 (US $0.10) per person per year (21),

Agrobotanical studies on ended in Ethiopia over

the last 5 years under a special grant from the

Netherlands Government have shown encouraging

results. According to Dr. Lugt and his Ethiopian

counterpart, Dr. Yohannes, selected strains of the

ended plant can produce about 1,500 kg berries/ha/

yr at the cost of about US $1,000 in local currency,

while the German product, Bayluscide, costs about

$25,000 per MT in foreign currency. Ended grown

on only about 1 hectare of land would treat 1,200

ha of irrigated sugar cane, for which 91,000 MT of

water per year are needed (4 I).

Where high-potency ended varieties (able to kill

snails at 5 ppm) can be harvested directly from local
Molluscicidal and Other Economic Potentials of Ended . 123

farms, the ground or pressed berries could be applied directly to streams and irrigation canals,

without need to concentrate or extract the molluscide. This would greatly reduce product and treatment costs.

Current Status of Research

and Projected Activities

Field and laboratory studies on ended are being

carried out in Ethiopia at the Institute of Pathobiology, Addis Ababa University. The Ethiopian Ministry of State Farms is collaborating with the Institute because of their interest in possible commercial farming of ended. The Ministry of Public

Health is interested in the field applications of endod for schistosomiasis control in selected localities. However, owing to extremely limited financial

resources available for such studies in Ethiopia, the

level and intensity of research activities are very

restricted.

During the period 1964 to 1974, molluscicidal and

other properties of ended were intensively studied

in Ethiopia, the Institute of Pathobiology in Addis

Ababa, the Tropical Products Institute in London

(8), the Stanford Research Institute in California (9),

the Department of Epidemiology and International

Health of the University of California in San Francisco (5), the Harvard School of Public Health in

Boston (22), the U.S. Public Health Service laboratory and field stations in Puerto Rico, and the U.S.

Naval Medical Research Unit (NAMRU-3) in Cairo,

Egypt (5). Investigations conducted in other institutions in the United States, England, St. Lucia, Brazil, Egypt, the Sudan, Tanzania, and Japan on molluscicidal properties of ended under different conditions helped characterize its biological activity

(5,46).

In addition to Dr. Bollinger’s studies, Dr. John

Lambert and colleagues at Carleton University and

Ottawa University in Canada plan to undertake

long-range toxicological and agronomic field studies on ended. The toxicological studies are intended

to develop ended as a Canadian-backed and registered pesticide for possible widespread use as a

molluscicide in different parts of the world. The

ecological and agricultural studies, particularly of

Dr. Lambert, involve the natural ecology of ended

and determination of optimal conditions for growth

and development of cloned plantlets, berries, and

cuttings of selected strains for adaptation to different countries including Ethiopia, Zambia, and

Swaziland, As a result of these recent developments, a renewed interest in ended is rapidly

spreading among African and other countries.

UNICEF has also shown interest in possible largescale application of ended for schistosomiasis and

other snail-borne disease control, especially with

regard to its use on a community self-help basis,

to be developed as part of UNICEF’s integrated basic health services delivery programs in rural areas.

The Zambian National Council for Scientific Research held an “International workshop on Phytolacca dodecandra” in March 1983, in Lusaka,

Zambia, to bring these interested individuals and

groups together, review work done on ended to

date, identify shortcomings, delineate gaps to be

filled, and develop specific areas and ideas for

future work. A group of about 30 scientists with

varying backgrounds from a number of African

countries, the United States, England, and Brazil

participated. The Lusaka meeting is expected to

lead to further collaborative work on ended by participating experts as well as on other plant products

and the control of schistosomiasis in general.

The benefits of ended go well beyond the potential applications of its many different properties,

however promising they appear to be. It sets an example of local development of a natural product for

multiple use that can be adapted to endemic social

and cultural systems, raise the level of group participation and confidence, and improve the local

and regional economy at minimal international cost

and hard currency expenditure. Ended’s major importance, however, is in the control of schistosomiasis and other trematode diseases.

1,

2,

3.

4.

5.

6.

Dalziel, J. M., The Useful Plants of West Tropical Africa (London: Crown Agents, 1936).

Watt, J, M., and Breyer-Brandwijk, M, G., The A4edicinaJ and Poisonous Plants of Southern and Eastern

Africa, 2d cd., (Edinburgh and London: E. and S. Livingston Ltd., 1962),

Lemma, A,, “A Preliminary Report on the Molluscicidal Property of Ended (Phytolacca dodecandra), ”

Ethiopian Med. J. 3:187-190, 1965.

Lemma, A., “Laboratory and Field Evaluation of the

Molluscicidal Properties of Phytolacca dodecandra,”

Bu]]. WHO 42:597-617, 1970.

Lemma, A., Heyneman, D., and Kloos, H., “Studies

on the Molluscicidal and Other Properties of the ENDOD Plant Phytolacca dodecandra,” Institute of

Pathobiology, Addis Ababa University and Department of Epidemiology and International Health, University of California, San Francisco, Calif., special

publication, 1979, 522 pp.

Lemma, A., and Yau, P., “Studies on the Molluscici-
124 . Plants: The Potentials for Extracting protein, Medicines, and Other Useful Chemicals—workshop Proceedings

dal Properties of Ended (Phytok+cca dodecandra),”

ch. 111 “Stability and Potency Under Different Environmental Conditions,” Ethiopian Med. J. 13:115-124,

1974.

7. *Jewers, K., and King, T. A., “Improvements Relating

to Molluscicides,” The Patent Office, London, Patent

No. 1277414, 1972.

8. *Lemma, A., Parkhurst, R. M., and Skinner, W. A.,

“Method of Producing a Molluscicide From Ended,”

U.S. Patent Office, Patent No. 3,813,3, 1974.

9. *Parkhurst, R. M., and Stolzenberg, S. J., “SaponinContaining Spermatocidal Compositions, ” U.S. Patent Office, Patent No. 3,886,372, 1975.

10. Kloos, H., and McCullough, F. S., Plant

Molluscicides: A Review, WHOlSchisto181:59, 1981.

11. McCullough, F. S., Guyral, P. H., Duncan, J., and

Christie, 1. D., “Molluscicides in Schistosomiasis Con12.

13.

14.

15.

16,

trol,” Bulletin of the World Health Organization

58:681-689, 1980.

Daffala, A. A., and Amin, M. A., “Laboratory and

Field Evaluation of the Molluscicidal Properties of

Habat-el-Mollok (Croton spp.),” East African J. Med.

Res. 3:185-195, 1976.

Yasuraoka, K., Hashinguchi, J., and Banez, E. A.,

“Laboratory Assessment of the Molluscicidal Activity

of the Plant Croton Tiglium Against Oncomelania

Snails, ” Proceedings of the Philippine-Japan Joint

Conference on Schistosomiasis Research and Control,

Manila, the Japan International Cooperation AgenCy, 1980, pp. 106-108.

Yasuraoka, K., Hashiguchi, J., and Bias, B. L., “Laboratory Assessment of the Molluscicidal Activity of

the Plant Jatropha Carcas Against Oncomelania

Snails, ” Proceedings of the Philippine-Japan Joint

Conference on Schistosomiasis Research and Control,

Manila, The Japan International Cooperation AgenCY, 1980, PP. 110-112.

Yasuraoka, K,, “Laboratory Evaluation of the Molluscicidal Properties of the Triterpenoid Saponin, a MolIuscicidal Fraction From Ended (Phytolacca dodecandra) Against Oncomelania nosophora, ” WHOI

Schisto171:8, 1971.

Medina. F. R,, and Woodburv, R., “Terrestrial Plants

Molluscicidal to Lymnaeid Hosts of Fascioliasis

Hepatica in Puerto Rico,” Journa~ of Agriculture of

the University of Puerto Rico 63:366-376, 1979.

17. E1-Sawy, M. F., Bassiouny, K., and E1-Magdoub, A.

1. “Biological Control of Schistosomiasis, Ambrosia

maritima (Damsissa) for Snail Control, ” Journal of the

Egyptian Society of Parasitology 11:99-117, 1981.

18. Lugt, C. B., “Development of Molluscicidal Potency

in Short and Long Staminate Racemes of Phytolacca

dodecandra, Planta medica,” Journal of Medical Plant

Research 38:68-72, 1981.

19. Gonnert, R., and Strufe, R., “Comparative Investigations of Some Molluscicides,” Proceedings of the Ciba

Foundation Symposium on Bilharziasis, Wolsten-

“~atented procedures.

20.

21.

22,

23

24.

holme and O’Connor (eds.), Little, Brown and Co.,

1962, pp. 326-338.

Lemma, A., and Yau, P., “Studies on the Molluscicidal Properties of Ended (Ph~oZacca dodecandra). II.

Toxicity of Various Molluscicides to Fish and Snails,”

Ethiopian Med. J. 12:109-114, 1974.

Lemma, A., Goll, P., Duncan, J., and Mazengia, B.,

“Control of Schistosomiasis With the Use of Ended

in Adwa, Ethiopia: Results of a 5-year Study,” Proc.

International Conference on Schistosomiasis, Cairo,

1978, pp. 415-436.

Spielman, A., and Lemma, A., “Ended Extract, a

Plant-Derived Molluscicide: Toxicity for Mosquitoes,” Am. J. Trop. Med. Hyg. 22:802-804, 1973.

Assefa, G., progress report, “Studies on the Insecticidal Property of Ended: Houseflies and Black Flies

(SimuZium sp.),” unpublished research note No. 16,

Institute of Pathobiology, 1976, PP. 203-205.

Flemings, M. B., “Effects of End~d on the PerisDi- .

racular- Glands in Larvae of Mosquitoes, ” unpublished report, C. W. Post College, Long Island

University, Brookville, N. Y., reference No. 5, 1975,

pp. 198-202.

25. Stolzenberg, S. J., Parkhurst, R. M., and Reist, E. J.,

“Blastocidal and Contraceptive Actions by an Extract

From Ended (Phytolacca dodecandra),” Contraception 14:39-51, 1976.

26. Stolzenberg, S, J,, and Parkhurst, R. M., “Spermicidal

Actions of Extracts and Compounds From Phytolacca dodecandra,” Contraception 1o:135-143, 1974.

27. Lemma, A,, Maxwell, A., and Brody, G., “Antimicrobial and Anthelmintic Activities of Ended (Phytolacca dodecandra), ” unpublished research note No. 12,

Institute of Pathobiology, reference No. 5, 1972,

pp. 153-159.

28. Lemma, A., and Ames, B. N., “Screening for Mutagenic Activity of Some Molluscicides,” Trans. Roy.

Soc. Trop. Med. Hyg. 69:167-168, 1975.

29. Mamo, E., “A Short Note on Toxicity Studies of Ended (Phytolacca dodecandra) on Sheep and Dogs,”

unpublished research note No. 5, Institute of Pathobiology, reference No. 5, 1977, pp. 246-247.

30, Getaneh, M., and Lemma, A., “Comparative Toxicity Studies of Three Molluscicides (Bayluscide, Frescon and Ended) to Microflora (Phytoplankton Species) and Microfauna (Zooplankton, Crustacea Species and Arthropoda-Insects) and Toxicity Study of

Ended, ” unpublished research note No. 4, Institute

of Pathobiology, reference No. 5, 1977, pp. 209-212.

31. Parkhurst, R. M., “Endod-Wonderweed of Africa,”

in reference 5, 1977.

32. Parkhurst, R. M., Thomas, D. W., Skinner, W. A., and

Cary, L. W., “Molluscicidal Saponins of Phytolacca

dodecandra: Lemmatoxin, ” Canad. J. Chem.

52:702-705, 1974.

33. Parkhurst, R. M., Thomas, D, W., Skinner, W. A,, and

Cary, L. W., “Molluscicidal Saponins of Phytolacca

dodecandra: Oleanoglycotoxin-A, ” Phytochem,

12:1437-1442, 1973.
Molluscicidal and Other Economic Potentials of Ended ● 125

.

34. Parkhurst, R. M., Thomas, D. W., Skinner, W. A., and

Cary, L, W., “Molluscicidal Saponins of Phytolacca

dodecandra: Lemmatoxin-C, ” Indian J. Chern,

11:1192-1195, 1973.

35. Powell, J. W., and Whalley, W. B., “Triterpenoid Saponins From Phyto]acca dodecandra, ” Phytochern.

8:2105-2107,1969.

36. King, T. A., Jewers, K., Richardson, H., and Falshaw,

C. P., “The Chemistry of Ended,” 5th Int. Symposium

on the Chemistry of Natural Products, London, July

1968, Abstract F-43, 1968,

37. Parkhurst, R. M., “The Chemotaxonomy of Phytolacca dodecandra, Indian J. Chem. 13:757-758, 1975.

38. Lemma, A., Brody, G,, Newell, G. W., Parkhurst, R.

M., and Skinner, W. A., “Ended (Phytolacca dodecandra) a Natural Product Molluscicide: Increased Potency With Butanol Extraction, ” J. Parasite]. 58:104-107,

1972.

39. Yohannes, Wolde, Lemma, T., Lemma, A., “New Approaches to Ended (Phytolacca dodecandra) Extraction,” SIIVET: Ethiopian J. Sci. 2(2):121-127, 1979.

40. Lemma, T., and Lemma, A., “Calorimetric Determination of Ended, ” unpublished research note No. 2,

Institute of Pathobiology, reference No. 5, 1977,

pp. 230-240.

41. Lugt, G. G., “Phytolacca dodecandra Berries as a

Means of Controlling Bilharzia Transmitting Snails,”

booklet published by the Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia, 1981.

42. Lugt, C, B., “Development of Molluscicidal Potency

in the Short and Long Staminate Racemes of PhytoZacca dodecandra, Planta Medica, “J. Medicinal Plant

Research 38:68-72, 1980.

43. Lugt, C, B., “Agrobotanical Studies on Ended,” Ethiopian Med. J. 16:140-141, 1978.

44. Michael, T. G., and Yohannes, L. W., “Preliminary

Report of the Investigation of Insect Pests of Ended

(Phytolacca dodecandra),” unpublished research note

No. 9, Institute of Pathobiology, reference No, 5, 1977,

pp. 247-251.

45. Wossen, C. G., and Lemma, A., “Antibacterial and

Antiprotozoan Properties of Ended,” unpublished

research note No. 13, Institute of Pathobiology, reference No. 5, 1977, pp. 258-259.

46, Balaawy, S., “Laboratory Evaluation of the Molluscicidal Potency of a Butanol Extract of Phytolacca

dodecandra,” Bull. WHO 47:422-425, 1972.

47. Roger, P. A., and Reymoud, P. A., “Free Living BlueGreen Algae in Tropical Soils,” Microbiology of Tropical Snails and Plant Productivity, Y. Dommergues

and H. Diem (eds.)(The Hague: Martinus Mizhoff Publisher, 1982), pp. 147-168.
CHEMICALS FROM ARID/SEMIARID LAND PLANTS:

WHOLE PLANT USE OF MILKWEEDS

Robert P. Adams*

Manager, Phytochemical Prducts, Native Plants, Inc.

Salt Lake

Abstract

The potential of arid/semiarid land plants a s

sources of commercial products is illustrated by the

following examples: candelilla (wax); jojoba (oil,

protein); Acacia spp. (gum); Astragalus spp. (tragacanth gum); guayule (rubber); rabbitbrush (rubber,

chemicals); sunflowers (rubber, chemicals); yucca

(soap); and cresote bush (antioxidants, phenolic

resins). co-evolutionary selection is a cause of the

accumulation of secondary compounds in arid and

semiarid plants. Although extraction of a single

chemical might prove economically feasible for a

few species, analyses involving extraction of multiple components and use of the extracted residue

show that significantly greater value can be obtained by fractionation to attain whole-plant utilization. Although efficient laboratory methods to

screen plants have been developed, only a few

chemicals can be screened in the field. Additional

research and development in field screening techniques are needed. Milkweed is a potential new

chemical crop. The present stage of development

is at the research, demonstration plot, pilot-plant

phase. Milkweed is expected to be grown as a dryland crop in the western Great Plains using conventional farming machinery now used in alfalfa

‘hay production. Large-scale plantation farming

would have an impact on imports of fuel and other

commodities, By providing an alternative cash crop

for the western Great Plains, milkweed farming

could greatly strengthen the agricultural economy

of the region.

Introduction

To illustrate the utility of obtaining chemicals

from arid/semiarid land plants, it is useful to examine some species that currently or potentially

could produce industrial raw materials. Candelilla

(fig. 1), Euphorbia antisyphilitica Zucc. (Euphorbiaceae), is the source of candelilla wax imported

from Mexico (13). The market is good, but imports

have dropped from 871 metric tons (MT) (960 tons)

in 1978 to 379 MT in 1981 due to internal problems

of procurement from native stands in Mexico. Candelilla wax sells for $4.19/kg ($1.90/lb) (16).

● Current address is Department of Botany, University of Texas, Austin,

TX 78712.

126

City, Utah

Figure 1

Candelilla Euphorbia antisyphilltica,a, In a natural stand in the Chihuahuan Desert

of West Texas and northern Mexico la a current source of high-valued wax

Jojoba oil is obtained from the seeds of Simmondsia chinensis (Link) Schneider (Buxaceae) in approximately 50 percent yield. This species is native

to deserts of northern Mexico and Southwestern

United States. The oil, composed of long chain esters that are stable under high temperatures, is

useful as a lubricant (24). At present essentially all

jojoba beans come from natural stands. The first

commercial harvest of 3-year old plants in the

United States is expected to be this year (1982).

Gum arabic is obtained from Acacia senegal (L.)

Wind. (Fabaceae) which is native to arid lands of

Africa and the Middle East (31). Acacia gum is used

in adhesives, bakery products, candies, ice cream,

cosmetics, and many foods to suspend solids and

emulsify ingredients (31). The United States imports approximately 5,080 MT annually (17). The

gum sells for approximately $1.57/kg (16). Over 100

Acacia species are known to exude gum. Acacia

berlanderi, native to southern Texas and northern

Mexico, appears to be a good candidate for a domestic gum source (31).

Another important gum (tragacanth) comes from

Astragalus gummifer Labill. (Fabaceae) and related

species. These Astragalus species grow in the high,

cold deserts of Iran and the surrounding area. Gum

tragacanth is used in pharmaceuticals, cosmetics,

and as thickening agents in foods (31). Due to the

political instability of the area, imports are erratic.

Approximately only 126 MT were imported last

year at a price of $83/kg (16). No other gum has been

found that is a substitute for tragacanth gum. The
Chemicals From Arid/Semiarid Land plants: Whole Plant Use of Milkweeds . 127

species seem to be well adapted to the high, cold

deserts of the Western United States,

Natural rubber can be obtained from guayule

(Parthenium argentatum A. gray (Asteraceae)), a

desert shrub from the Chihuahua desert of northern Mexico and west Texas (13). Its molecular

weight is comparable to that of Hevea brasiliensis

Mull. (44). The United States imports approximately 770,000 MT/year of natural Hevea rubber, principally from Southeast Asia (39). Guayule rubber

production in Mexico reached a peak from 1941 to

1945 with approximately 36,400 MT being exported

from Mexico (13). Natural rubber prices are about

$0.95/kg (47). T WO other sources of natural rubber

are rubber rabbitbrush (Chrysothamnus nauseosus

(Pall,)) Britton (21) (fig. 2) and sunflowers (Helianthus species) (40,41), all in the Asteraceae family.

Soaps for shampoos are being extracted from various species of Yucca (Liliaceae) (13). Biologically

active compounds are obtained from many plants,

the most familiar of which are morphine (opium)

from Papaver somniferum L. and digitalis from

Digitalis purpurea L. (46). Larrea tridentata (DC.)

Coville (Zygophyllaceae), the creosote bush, is a

potential source of nordihydroguaiaretic acid

(NDGA) which maybe used as an antioxidant (28)

and in the production of phenolic resins (13).

Chemicals mentioned in the examples above generally are considered not involved in the primary

metabolism of plants and are referred to as secondary compounds. It is now becoming apparent that

secondary compounds may be of considerable importance to the survival of plants (37). Some secondary compounds repel deer (35), deter browsing

by hares (8), and act as toxic and feeding deterrents

in insects (42).

Herbivores can be divided into specialists and

generalists. The specialist herbivores often prefer

Figure 2

Chrysothamnus nauseosus,rubber rabbitbrush, from Nevada, is a future source

of industrial chemicals and natural rubber

young leaves or rapidly growing tissue, whereas the

generalists tend to prefer mature leaves and tissue

(14). The generalists browse many different species,

often over a considerable part of the year. Plants

growing in arid lands can be subdivided into annuals, which take advantage of infrequent rains to

grow to maturity and set seed quickly, and perennials, which have various adaptations enabling

them to survive throughout the year. Major adaptations for drought survival are succulence (e.g.,

cactus), long roots to reach deep water tables (e.g.,

mesquite), and deciduous leaves during winter because many insects and animals may be inactive.

Long-lived perennials need not reproduce every

year, but they must survive drought, insects, diseases, and animal predation ultimately to reproduce, The evolution of environmental protection

and more efficient metabolic processes is pitted

against the relatively predictable selective forces of

climate: natural variation in rainfall, wind, heat,

and desiccation. In contrast, evolution of plant

chemical defenses races constantly with the predator in a co-evolutionary battle,

After a plant evolves a new chemical or morphological defense, selection begins to operate on the

predators that have mutations allowing them to

overcome the plant defense. Perennial arid land

plants tend to have morphological defenses (e.g.,

spines in cactus) and/or chemical defenses (e.g., bitter tasting phenolics in creosote). In more mesic regions, the species commonly can tolerate considerable browsing because adequate moisture is available for regrowth. As this is not the case in arid

lands, it appears that accumulation of secondary

products in arid land plants is necessary for survival. Since arid land plants have evolved and coevolved defenses for millions of years, these species

are important for the discovery of fungicides, insecticides, and herbicides and as sources of accumulated secondary compounds.

Some major problems of growing plants in arid

lands are that: biomass per area is low and harvesting costs may be expensive; wind and water soil

erosion is already severe, so crops will have to be

managed carefully; and a monoculture of an arid

land crop, as with any crop, may allow the natural

predators to increase,

Although initial emphasis may be on a single

chemical or class of chemicals, few potential crops

seem to be economically feasible if only a single

product is obtained, Due to the costs of growing,

harvesting, and extracting chemicals, each species

should be examined for multiple uses (1,12). After

the plant material has been collected at a central

processing facility, the additional cost to process
128 ● Plants: The Potentials for Extracting Protein, Medicines, and

the material by several methods to extract additional products may not be large. For example, candelilla produces a fine wax, but this only accounts for

12 to 15 percent of the biomass. Cellulose from the

remaining 85 to 88 percent can be used in fermentation or as an animal feed.

In general, nonpolar solvents extract chemicals

that might be useful as waxes, lubricants, and elastomers. Polar solvents extract compounds that may

be more useful as chemical intermediates, since

they may contain highly reactive oxygen groups.

They may be used as adhesives, coatings, UV absorbers, antioxidants, dyes, etc. The polar fraction

has the greatest concentration of biologically active

compounds (3).

The water or acidic aqueous fraction may yield

a gum, such as tragacanth, or other valuable poly -

saccharides, such as pectin. Some water-soluble

protein may be recovered at this step. The principal

products left after extraction are cellulose, hemicellulose, lignin (if present), and protein. This

residue can be nontoxic if biologically active compounds have been extracted previously. The residue may be used in several ways. Some of it may

be burned to generate power at the processing

plant. It may be burned in power generation stations in place of coal (12). Fiber may be removed

during processing for use as paper, pulp, or fabric.

The residue usually has an enriched concentration

of protein and may be used as livestock feed. It

could also be digested by fermentation to produce

industrial chemicals (32).

Species with high yields of particular chemicals

generally have been identified by solvent extraction

in the laboratory (4,5,9,10,29). Field screening is extremely valuable once a selection program has begun. A rapid method to screen plants in the field

would allow one to examine hundreds of plants per

day and obtain seeds and cuttings immediately.

Otherwise, each plant must be sampled and tagged.

After the laboratory analysis, one must return to

the field and find the desired individual. The plants

may be from a remote site. The time lapse from the

initial tagging through laboratory analysis to returning for germ plasm collection can span months or

even a few years. In the meantime, the tags may

be lost to wind or animals. Germ plasm could be

collected at the time of initial sampling, but this

necessitates collection and curing of a large volume

of materials, 90 percent of which subsequently will

be discarded. Collecting, preserving, and documenting field samples are time consuming activities and are major obstacles in massive screenings.

Two relatively new laboratory techniques have

been developed for rapid screening: wide-line nuOther Useful Chemicals— Workshop Proceedings

clear magnetic resonance (NMR) and near-infrared

reflectance (NIR). Wide-line NMR is used in vegetable oil yield analysis because it specifically

measures total hydrogen associated with only the

liquids (oil and water) (36). Because NMR is nondestructive to oil seeds, plant breeders have used

this technique extensively, Wide-line NMR is not

portable enough for field screening and seems to

be limited to liquid chemicals. NIR has a much

broader potential range of applications. It has been

used principally for seed oil and protein analyses

(23,38). The plant material must be uniformly

ground and its moisture content determined. NIR

is, therefore, destructive of plant materials, although this is not a problem for whole plant chemicals. Field portable NIR units are available, but approximately 50 samples are needed for calibration

on the large laboratory system to determine the optimum wave-length filters and regression equations.

To my knowledge, Native Plants, Inc., is the only

group that has tried to use NIR to predict the yield

of a mixed group of chemicals—in particular, hexane and methanol extractable. Our results were

not satisfactory. Further research is needed in this

area.

Another method of field screening would be

micropressure extraction coupled with a portable

microwave oven and sensitive electronic field balance. Although this method probably is feasible, to

my knowledge no one has developed such a system.

One major difficulty in developing a field screening technique is that chemicals of interest may not

have unique spectral qualities or any reactive

groups to which specific stains can be applied for

color tests. The polar chemicals are more likely to

have strong spectral properties and unique color

reactions with reagents. For example, a color test

for alkaloids is quite specific and relatively easy to

do. However, a specific color test for only one alkaloid in a family may not be possible.

In summary, adequate field screening techniques

for chemicals are not available. This is a serious

obstacle to future development of chemical crops.

As part of a long-term study to discover new

crops for production of phytochemicals, Native

Plants, Inc., has been studying the showy milkweed

(Asclepias speciosa Torr.) (fig. 3). The genus

Asclepias includes approximately 140 species

(48,49). All cytologically known species are diploids. Interspecific hybridization is reported to be

extremely rare in spite of widespread self-sterility
Chemicals From Arid/Semiarid Land Plants: Whole plant Use of Milkweeds ● 129 —

Figure 3

A test plantation (5 ha) of showy milkweed, Asclepias speciosa, near Syracuse,

Utah

(49). The North American species generally are

erect, herbaceous perennials, although a few annuals are known (48).

No rhizomatous North American species are

known except A. syriaca which “may produce gemmiferous roots giving rise to clones of limited extent” (48). However, rhizomatous growth has been

observed in A. latofolia (R. Adams, observation).

Asclepias tuberosa is reported to live over a century (48).

Due to the wide distribution of A. speciosa and

its apparent ecological success, this taxon was selected for intensive research on its domestication

potential as a source of phytochemical products.

Asclepias speciosa, the showy milkweed, is widely distributed from near the Mississippi River westward to the Pacific coast and from central Saskatchewan and Alberta south to central Oklahoma, West

of the Rocky Mountains, it is chiefly found along

banks of irrigation ditches. It produces a feathery

plume on the seeds which are easily dispersed, In

Minnesota, the northeastern part of its range, it

competes with crops and can cause significant

problems.

Milkweed Products

Hexane extracts of the aerial parts of A. speciosa,

obtained by Soxhlet extraction for 20 hours, are

dark green. The pigments are removed by decoloring (11), and natural rubber (cis-1,4-polyisoprene)

can be removed by acetone precipitation followed

by centrifugation. The decolonized, rubber-free hexane extracts have been subjected to analysis by thin

layer chromatography (TLC) and glass capillary gas

chromatography (GC) and gas chromatography

mass spectroscopy (GC/MS) (in Tri-Sil ‘Z’; Pierce

Chemical Co.). Over 90 percent of the constituents

of the hexane extracts could be identified and quantitated in this manner (2,3).

Pigments, mainly chlorophylls, account for approximately 11 percent of the hexane extract, and

low molecular weight rubber accounts for approximately 2 percent of the extract (table 1). The nonpolar extracts contain small amounts of fatty acids,

alcohols, hydrocarbons (alkales and squalene),

monoglycerides, and phytosterols. Cardenolides

were not detected in the hexane extract by TLC

using the Kedde reagent for visilization (2). Approximately 85 percent of the nonpolar extract consists

of derivatives of ~- and ß-amyrin related triterpenes (2). Over 60 percent of the decolonized, rubber-free hexane extract consists of CY - and ß-amyrin

acetates, present in a ratio of about 5:1. Smaller

amounts of the corresponding butyate, caproate

(hexanoate), and palmitate esters of these triterpenes were found in roughly the same ratio of ~-

to ß-derivates.

The methanol extract of the aerial parts of A .

speciosa following hexane extraction consists chiefly of inositol and sucrose (table 1). Other minor constituents identified by GC/MS in the methanol extract include malic acid, pyroglutamic acid, methyl

pyroglutamate, citric acid, proline, methyl ferulate,

and trace quantities of numerous carbohydrates.

True phenolics account for only a minor part of the

methanol extract, so A. speciosa does not seem to

be a promising source for the economic extraction

of “polyphenols” (table 1). Low polyphenol content

has previously been reported for A. syriaca (20).

Also present in the methanol extract of A. speciosa are small quantities of cardenolides (demonstrated TLC using the Kedde reagent). Plants in the

genus Asclepias biosynthesize varying amounts of

toxic cardenolides (7). Aside from their digitalis-like

toxic effects on the heart, cardenolides from Asclepias species affect the lungs, kidneys, gastrointestinal tract, and brain of experimental animals

(6,7,22,34). They also possess general cytotoxic activity (26,27).

An additional acidic aqueous extraction of milkweed yielded approximately 4 percent pectin, a cell

wall constituent present in all higher plants (3). Pectin is a valuable product ($3.91/kg) (16) but is difficult to extract and purify.

The milkweed residue, after exhaustive extraction with hexane and methanol, seems to be nontoxic and equivalent to alfalfa hay in digestibility

by sheep (18). In research carried out by Native

Plants, Inc., Asclepias speciosa was harvested in

full flower (June 26, 1981) and extracted with hex-
130 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Table 1.– Proximate Analyses and Product Values of Milkweed

Value Product value from

Product % Yield $/kg ($/lb) 1 MT (t)

Hexane extract

Pigments

Natural rubber

Tri-terpenoids, esters

and related compounds

Methanol extract

Sucrose

Inositol

Polyphenolics

Residue

Pectin

Fibers

Livestock feed

3.8

0.4

0.1

3.3

17.5

6.0

0.9

1.1

4.0

5.0

70.0

Total gross value

per MT (t)

o. 22(0. lo)*

0.95(0.43) +

O. 24(0.11)*

3. 30(1. 50)+

0.68(0.31 )

24.00(10.90)

0. 13(0.06)*

O. 55(0. 25)+

3.91 (1. 78)

0.47(0. 21)

0.09(0.04) x

O. 13(0. 06) Y

Low

High

O. 88(0. 80)*

o. 95(0. 86)+

7.92(7.19) *

108. 90(98. 82) +

40. 92(37 . 13)

216.00(196.00)

1 ● 43(1 . 30) *

6. 05(5. 60)+

156.40(141 . 92)

23. 50(21 . 32)

63.00(57.17)x

91.00(82. 58) Y

511 ● 00(463. 70)

644. 60(584. 94)

*Price based on Btu Content.

+Price based on substitution for an appropriate chemical feedstock

‘Price based on low hay value.

Yprice based on high hay value.

SOURCE: Adams, etal, 1983; Adams, Balandrln, and Martineau,1983. Prices: Chem. MkL Rptr., Nov.8, 1982, and Wa// Street JournaL Nov. 1, 1982.
Chemicals From Arid/Semiarid Land Plants: Whole Plant Use of Milkweeds ● 131

ane/methanol. The residue contained 16.3 percent

crude protein (N X 6.25), which is similar to alfalfa

hay (16 percent) and greater than corn grain (9.7

to 10 percent) (1). Amino acid analysis of the sample revealed that the amino acid content is comparable to alfalfa and generally superior to corn grain

(l). The protein has high amounts of lysine (280 percent of the corn value) and a greater concentration

of the essential amino acids than corn (1).

All toxic constituents in showy milkweed could

be removed by exhaustive methanol extraction. The

feasibility of using showy milkweed as an animal

feed, therefore, depends on detoxification of the

residue, either by high extraction efficiencies, heat,

or acid treatment. The detoxification of the residue

must be established by feeding trials.

The total gross value of products that could

be obtained from nonselected (wild) A. speciosa

ranges from $511/MT to $645/MT. Unfortunately,

several technological problems need to be solved

before its commercial potential can be realized.

Commercially viable extraction and purification of

the two highest value products, inositol and pectin, have not been demonstrated. Both products are

expensive because they are difficult to extract and

purify. In addition, inositol and pectin have limited

markets: inositol, 0.45-0.9 million kg (R.W. Greef

& Co., pers. comm.); pectin, 1.6-1.8 million kg (15).

If the technology is developed, demand for these

products could support a small 6,000-ha plantation,

but could not sustain unlimited sized plantations

as would be the case for some petrochemicals.

All current extraction processes for milkweed use

hexane followed by methanol in a conventional extractor, such as the Crown extractor. To date, two

proto-commercial extractions have been made, one

at the POS (Protein-Oil-Starch) pilot plant at the

University of Saskatchewan and the other at the

Northern Regional Research Center, ARS, USDA,

in Peoria, Ill. Extraction efficiencies at the POS

Pilot Plant were only 67.5 percent for the hexanesoluble material and 55.7 percent for the methanolsoluble material (18), Problems were encountered

with fine particles plugging the system and in

pumping the viscous hexane extract after partial

solvent removal. Additional research is needed on

grinding, particle sizing, extract handling, and extraction residence times. Research also is needed

on decolonizing the hexane extract and separating

rubber from triterpenoids. As previously mentioned, considerable technological! development is

needed before the production of inositol and pectin is commerically feasible. More efficient methods

are needed for detoxification of the livestock feed.

Agronomics

The optimum planting methods for milkweed are

not well known. Native Plants, Inc., has successfully established a 4-ha plot in Utah and small test

plots in New Mexico, Texas, and Kansas. We have

experienced establishment failures in Texas, Utah,

and Saskatchewan, Canada, Additional research is

needed on depth and time of planting. Density trials

have indicated that a closed canopy yields higher

biomass.

Wood Control

Weed control is a major problem with milkweed,

especially during stand establishment. During the

seedling stage, milkweed seems to direct most of

its energy into root development. This contributes

to drought tolerance, but the above-ground portion

grows slowly and is not competitive with fast growing weeds during the first year after establishment.

A selective, pre-emergent herbicide must be developed for use during the first year. In the absence

of such an herbicide, Roundup® was used prior to

emergence to control hard-to-kill perennials such

as salt grass (Distichlis stricta) and common mallow

(Malva neglecta). A wick applicator has been used

to apply Roundup® to control the taller weeds during the season. Weed control is perhaps the most

critical research need for the economical production of milkweed.

All of the equipment used in growing milkweed

is standard farm equipment readily available to

Figure 4

Harvesting of milkweeds uses conventional farm equipment for cutting, crimping, and baling
132 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings — —

western farmers. Harvesting has been performed

with equipment used in alfalfa haying operations.

Harvesting techniques are essentially the same for

milkweeds as for alfalfa hay.

A. speciosa test fields, 2 ha (5 ac) planted in rows

91 cm (36 in) apart, were first harvested on June

26, 1981. The plants were cut and crimped with a

hay conditioner and swathed into windrows. Stems

were dehydrated to a dry crack stage and baled

within 3 days. The leaves dried considerably faster

and became brittle. Some losses due to leaf shatter

occurred during baling. Hay that fell into the furrows between rows could not be picked up by the

baling machine, resulting in additional crop loss.

In 1982, our two fields of 2 ha each averaged 4.35

MT/ha and 4.26 MT/ha, respectively. Annual precipitation in the area is approximately 50.4 cm.

Denser stands are expected to yield between 6.7

MT/ha and 9.0 MT/ha.

Crop Storage

There would be a considerable economic savings

in plant capacity if an energy/chemical crop could

be stored and processed throughout the year. Two

apparent methods for storage are fresh-cut as silage

(70+ percent water) and dried as hay (15 to 20 percent water, fig, 5). Because both procedures use existing farm equipment, they would not require extensive new equipment or costly acquisitions by

farmers.

Native Plants, Inc., carried out some tests on the

effects of storing milkweed. Five bales were stored

uncovered under ambient conditions. This storage

test presented the worst possible conditions. The

bales were subjected to several feet of snow in the

fall and winter and a number of freezing and thawFigure 5

Milkweed Is stored in conventional bales until processed for the removal of

chemicals

ing cycles. The nonpolar extractable were found

to be quite stable over time. For example, the nonpolar extracts of the March sample after 8 months

of storage (3.75 percent ± 2 (0.116)) were not significantly different from the first month’s sample

taken in August (4.07 percent ± (0.072)). The methanol extractable, however, showed a sharp decline

after 2 months of storage and a gradual decline

thereafter. This decline probably is due to the catabolism of carbohydrates by microorganisms during

the rotting.

Three additional storage conditions have been

studied: bales stacked in a barn; bales stacked in

the open and covered with clear plastic; and bales

stacked in the open and covered with black plastic.

The nonpolar extractable yields show no significant

differences. The methanol extractable yields decreased only slightly.

In general, it seems that moisture and subsequent

rotting are the major potential problems associated

with storage of baled milkweeds. This generally is

not a problem in semiarid lands. In moister areas,

the bales could be covered with either clear or black

plastic.

Agricultural Scale

A survey of vegetable oil processing facilities revealed that processing plants range in capacity

from 91 MT/day to 1,090 MT/day. An extraction

plant with a capacity of 91 MT/day would process

27,300 MT/year, given the current yields from wild

milkweed (4.3 MT/ha) and assuming a processing

season of 300 days/year. This would require a

6,349-ha plantation. If 100 percent of this area were

planted, it would represent a block approximately

8 km x 8 km. If only 25 percent of the area were

planted to milkweed, the plantation would be equivalent to a 16 km x 16 km block, with a maximum

haul distance to a centrally located plant of 11.31

km. This compares favorably to current maximum

haul distances on the western Great Plains for grain

and ensilage (24 to 32 km.).

Milkweed (A. speciosa) is distributed widely over

a range of climate and soils. It appears that milkweed can be grown easily in the western Great

Plains of the United States. This area is mining

water from the Ogallala aquifer, and water shortages are resulting in a steady reversion from irrigated to dryland farming (43). The introduction of

a new dryland crop will compete for land with dryland wheat, grain, sorghum, and sunflowers. However, this land is not very productive and the dryland crops contribute only a small portion to total
Chemicals From Arid/Semiarid Land Plants: Whole Plant Use of Milkweeds ● 133 —

U.S. production of these crops. The cost of farming milkweeds eventually may be comparable to

farming dryland alfalfa. The first year of growing

milkweeds has been difficult due to the lack of an

effective method of weed control and problems in

stand establishment and obtaining a uniform stand.

In order to displace dryland wheat or grain sorghum, the new crop must be more profitable for

the farmer. An examination of yields and prices (45)

of Hansford County, one of the most productive

counties in the northern plains of Texas, shows the

precarious position of present farming units. The

average dryland yield of wheat for Hansford County for 1976 through 1980 was only 30.4 bu/ha (824.5

kg/ha) and the gross income was only $104.89/ha

(table 2). The economics of grain sorghum is similar; the average yield was 1,508.8 kg/ha, which

returned an average of $135.44/ha. If one could introduce a new crop that costs approximately the

same as dryland wheat or grain sorghum to grow,

the gross revenue needed to displace one of these

crops probably would be about 20 percent greater

than the present gross income of $135, or $162/ha.

Table 3 shows the variable production costs in

1982 for a 2-ha field in Syracuse, Utah. Based on

4.5 MT/ha using “wild” milkweed seed, the production costs were $418.45/ha or $92.99/MT. Of the

$418.45,$233.13 was spent on weed control. More

economical weed control is a priority for reducing

milkweed farming costs. The other large expenditure was harvesting. Because relatively small farm

equipment and small bales (30 kg) were used, conversion to larger swathing equipment and to stack

loader bales or round bales (450 kg) could represent

a considerable cost reduction. In any case, dryland

milkweed cannot be grown as cheaply as dryland

wheat or grain sorghum. On the other hand, the

products obtained from milkweed promise to be of

much greater value than those from wheat or grain

sorghum after efficient processing technology is

developed, One should also note that the cost drops

from $92.99/MT to $53.85/MT if yields can be increased from 4.5 to 9.0 MT/ha (table 3). Research

in breeding, selection, and agronomic development,

resulting in increased yields, will have a positive

impact on the profitability of milkweed.

Impacts

The development of a new crop which does not

compete directly for a market share with the traditional food/fiber crops (e.g., wheat, corn, grain

sorghum, soybeans, sunflowers, cotton, etc.) could

free the U.S. farmer from his dependence on proTable 2.–Yields and Gross Income From Dryland Wheat and Grain Sorghum in Hansford County, Tex., for 1976-80

Wheat Grain Sorghum

Yield Price/ Gross Income/ Yield Price/ Gross Income

Year bu/ha bu ha lb/ha lb ha

1976 21.0 3.17 $66.57 3326.0 .0355 $118.07

1977 19.8 2.14 42.37 3019.6 .0315 95.12

1978 3.9 2.92 8.76 2236.3 .0392 87.66

1979 61.0 3.82 233.02 5779.7 .0438 253.15

1980 46.7 3.72 173.72 2273.3 .0542 123.21

Avg.

Yield 30.3 (= 824.5 kg/ha) 3327.0 (= 1508.8 kg/ha)

Avg. Gros s

Income/ha $104.89 $135.44

SOURCE: Texas Department of Agriculture, 1981
134 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

— —

Table 3.—Variable Production Costs for Milkweed in the Second Year of Production at Syracuse, Utah, 1982,

1 Harvest (4.5 MT/ha, or 2 t/ac) and Prorated Costs @ 9 MT/ha (4 t/ac)

Basis: Rates a n d costs Prorated Costs

Variable Cost Materials @ 4.5 MT/ha @ 9 MT/ha

Herbicide 2.5 gal/ha Roundup @

$72.00/gal. 180.00 180.00

Spray

Swath

Bale

Pickup and

Haul Bales

Ferti1izer

Spread

Fertilizer

Herbicide

Spray

Machine and labor,

$6. 18/ha 6.18 6.18

Machine and labor,

$22.41/ha 22.41 22.41

$12. 10/MT, 4.5 MT/ha 54.45 108.90

34.50

22.51

69.00

45.02

&23/bale x 150/ha

80.4 kg/ha (160.8 kg/ha)

34-O-O @ 0.28/kg

Machine and labor,

$6. 18/ha 6.18 6.18

0.93 gal/ha Paraquat

@ $44/gal 40.77 40.77

Machine and labor,

$6. 18/ha 6.18 6.18

Total Variable Costs/ha 418.45 484.64

Cost/MT 92.99 53.85

SOURCE: DOE Final Report, 1982.

ducing surplus commodities. The major milkweed ●

products would have an impact on the following

markets:

●

●

triterpenoid: could substitute for oil imports if

converted to fuel or used for a lubricant, or for ●

foreign wax imports if converted to fuel or

used as a wax.

sucrose: could substitute for foreign, and pos- ●

sibly some domestic, sugar markets, although

only a small impact would be anticipated in

this high-volume market. ●

inositol: could substitute completely for imported inositol; all inositol currently is imported, mostly from Japan, with lesser amounts

from China.

pectin: could substitute completely for domestic and imported pectin, apparently now all

produced from citrus peels.

fiber: could compete with Douglas fir, tamarisk, and other woods for the paper-pulp market; impact probably would be insignificant.

livestock feed: could compete with corn ensi-
Chemicals From Arid/Semiarid Land Plants: Whole Plant Use of Milkweeds ● 135 —— —. —

lage, alfalfa, hay, possibly small grains. Impact

could be considerable, particularly since the

western Great Plains is a center of cattle feeding operations. The local cattle feed (grain

corn, corn ensilage, grain sorghum) has been

produced with water from the Ogallala aquifer

which is being depleted (43). A replacement

source of cattle feed will be important for survival of western Great Plains feedlots.

Development of milkweed as a crop will have a

positive economic impact on agriculture of the

western Great Plains. With essentially stable grain

prices and increasing operating costs, the farming

economy of that region is severely depressed and

many farmsteads may fail soon.

The current strategy for the establishment of a

commercial milkweed plantation is to encourage

a large company with sufficient financial resources

to contract the required amount of land (6,400 ha)

to be planted and harvested. The company would

begin construction of the processing plant with the

appropriate lead time, Each farmer probably would

be offered a guaranteed profit or gross price per

hectare, depending on the company’s confidence

in the projected growing costs and yields of

milkweed. The first year’s contract would be a total

expense for the company and would have to be prorated over several years’ income. After a few years,

the company would probably begin to pay the farmer on a per-ton basis to encourage farming efficiency. Since it is likely that milkweed will produce

several products, the market’s risk would be buffered. Ultimately, if products are obtained that feed

into fossil fuel related markets, it is conceivable that

many millions of hectares will be farmed with milkweed or similar crops. This would have some impact on U.S. wheat and grain sorghum production,

but considerable idle land is available for growing

these traditional crops if the price increases sufficiently. Since 80 to 90 percent of our grain production is used for livestock feed, the loss of the

dryland wheat and grain production in this area

would have to be compensated by production of

livestock feed as a byproduct of the operation. For

example, suppose a farmer who produces an average of 1.35 MT/ha of wheat begins to grow 4.5 MT/

ha of milkweed. The wheat has approximately 11

to 14 percent protein. After extraction, the yield of

milkweed residue would be 3.15 MT/ha (70 percent

of 4.5 MT/ha) (table 1) of 12 to 16 percent protein

livestock feed, Even if the extractable yield were

increased to 50 percent, the residue would equal

2.25 MT/ha of 12 to 16 percent protein livestock

feed. Thus, the battle between food and fuel (or

chemicals) can be muted effectively if crops are

developed that contribute significantly to livestock

feed. Only a small portion of grain produced is used

for human consumption, so the vast grain producing area from central Kansas eastward through

Iowa, Illinois, Indiana, and Ohio still could produce

all our necessary food grain.

The principal constraints to developing such a

system are scientific and economic factors. Selection and breeding are needed. Extraction and processing technology must be developed. There is a

need to continue research on product development

and industrial use. Establishing a plantation and extraction facility will be expensive. Native Plants,

Inc., is working with a major oil company that has

the resources to initiate such a venture. Few corporations will have both the resources and the desire to enter into this technology.

Many environmental constraints were considered when selecting milkweed as a potential crop.

These include drought, wind, heat, cold tolerance,

and soil constraints. A major concern in the western Great Plains is soil erosion, particularly by

wind. This could be a severe constraint unless adequate stubble is left in the field to prevent wind and

water erosion. Strip harvesting could assist with

erosion control. Leaving stubble in the field would

also help compensate for the loss of soil humus by

continued cropping. The problem of a general decline in critical soil minerals may be alleviated partially by recycling manure from the cattle feedlots.

Sustainability of the Resource Base

The rapid loss of irrigation water from the Ogallala aquifer in the western Great Plains (43) signals

a potential change in the agricultural output of this

region. The proposed new crop will be grown dryland in that region, so will not have a significant

impact on ground water resources. Growing milkweed may affect the local farmer. For example, because bees obtain nectar from milkweed flowers,

the potential exists for development of a honey bee

industry. Monarch butterfly larvae feed on milkweed. It is anticipated that these populations will

increase. Aphids are a serious pest on milkweed

and probably will be controlled by both natural

predators and insecticides. As already mentioned,

soil fertility will decline, approximately in proportion to the amount of biomass removed. Nitrogen
136 . Plants: The Potentials for Extracting protein, Medicines, and Other Useful Chemicals—Workshop Proceedings —

is one of the principal elements that will have to

be replaced.

In general, our goal is to promote an ecologically sound approach to land and crop management.

Growing milkweed and other plants that are

adapted to arid and semiarid conditions offers an

unusual opportunity to apply a biorational approach to new crop development on lands with a

limited water supply. The constant process of coevolution of plants with other plants, insects, and

animals provides a great untapped source of phytochemicals for industrial chemical feedstocks.

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Chemicals From Arid/Semiarid Land Plants: Whole Plant Use of Milkweeds ● 137

30. National Academy of Sciences, Underexploited Tropical Plants With Promising Economic Value, Washington, D. C., 1975.

31. National Academy of Sciences, Tropical Legumes:

Resources for the Future, Washington, D. C., 1979.

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213:513-517, 1981.

33. Peoples, T. R., Alcorn, S. M., Bless, H. E., Clay, W.

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“Analysis of Forages by Infrared Reflectance,” Dairy

Sci. 62:807-812, 1979.

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Handbook Marketing Research on Natural Rubber,

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INSECTICIDES, INSECT REPELLANTS, AND ATTRACTANTS

FROM ARID/SEMIARID-LAND PLANTS

Martin Jacobson

Biologically Active Natural Products Laboratory

U.S. Department of Agriculture, Beltsville, Md.

Four weeds (Acorus calamus, Artemisia tridentata, Heliopsis longipes, and Tagetes minuta) and

three cultivated plants (Azadirachta indica, Mammea americana, and Ocimum basilicum) are potential candidates for crop development and commercialization for sources of insect attractants, repellants, or toxicants. Although all could be commercially viable, the neem tree (A. indica) is by far the

most likely to succeed. Its development in the

Southern United States and Central and South

America is highly recommended.

The plant kingdom is a vast storehouse of chemical substances manufactured and used by plants

as defenses against insects, bacteria, fungi, and

viruses, The American Indians and native tribes in

Central and South America, Asia, and Africa have

used and, in some places, still use decoctions from

many plants as medicines for a wide variety of ailments (30). The efficacy of these materials for relieving pain and suffering is described by Ayensu (5)

in the introduction to his “Plants for Medicinal

Uses With Special Reference to Arid Zones.”

Dioscorides (A.D. 40-90) divided poisons into

three classes: animal, plant, and mineral. He listed

opium, black and white Hyoscyamus, Mandragora,

Conium, elaterin, aconite, and the juices of Euphorbia species as plant poisons. He was also aware of

colchicum’s medicinal properties. The Remans

used Veratrum album and V. nigrum as medicines,

constituents of “rat and mice powders, ” and insecticides. From the time of the early Remans to the

20th century, only three efficient insecticides were

discovered: nicotine, pyrethrum, and hellebore.

The discovery of rotenone and several other plantderived insecticides followed in rapid succession.

Today, a wide variety of plants has been shown to

be effective not only as insect toxicants but also as

repellents, feeding deterrents, attractants, inhibitors of growth and development, and sterilants.

Useful general references on the subject of plantderived physiologically active materials for insects

are those by Jacobson and Crosby (24), Feeny (11),

Kubo and Nakanishi (31), Finch (12), Jacobson

(20,22), and Smith and Secoy (50).

Although arid/semiarid land plants do not produce compounds that are more biologically active

against insects than other plants, they lend themselves more readily to mass cultivation than plants

requiring fertile soil for growth and development.

Since promising pesticidal plants are too numerous to mention here, only the seven with the most

commercial potential are discussed. The scientific

name, common name (if known), and family of each

plant are given, followed by a discussion under the

following headings: description, native range, present and potential uses, active compounds, extraction, cultivation, and constraints to development.

Acorus calamus L.

Common names: Calamus, sweetflag

Family: Araceae

Description: A. calamus is a semiaquatic, robust

perennial that can grow on dry land, is 1.5 to 1.8

m (5 to 6 ft) tall, has a horizontal rootstock containing aromatic cells and iris-like leaves, and grows

at an altitude of 900 to 1,800 m (3,000 to 6,000 ft).

It is winter-hardy and flowers in early summer.

Native range: The American variety grows wild

in various provinces from Florida to Texas, Idaho,

Ontario, and Nova Scotia. The Indian variety is indigenous to the plains of India and Burma, Ceylon,

and the Celebes Islands. The Japanese variety occurs throughout the country. The European variety occurs throughout the continent.

Present and potential uses: The roots have been

used from ancient times in India and Japan for the

treatment of a variety of ailments and as an insect

repellent and toxicant. The essential oils from the

roots of the Indian and European varieties are obtained by steam distillation or solvent extraction of

the crushed rhizomes. These oils, reported to be

repellent and toxic to clothes moths, house flies,

fleas, several species of mosquitoes, lice, and several species of stored grain insects, are available

commercially, When the finely powdered rhizome

is mixed with various grains in a ratio of 1:50 (0.9

kg to 45.5 kg) the grains are free from insect damage

for a year. The dried rhizomes and leaves, as well

as their water infusions, are effective against crop

pests such as plant lice and beetle grubs (18,19). The

138
Insecticides, Insect Repellents, and Attractants From Arid/Semiarid-Land Plants ● 139

Indian root oil, which is obtained in 5 to 10 percent yield, is much more active than that obtained

from the Japanese variety which is obtained in less

than 1 percent yield. The oil causes sterility in male

house flies, and low concentrations hamper the

maturation of ova and cause complete regression

of the ovaries. The Indian oil, and to a lesser extent the European oil, is highly attractive to female

Mediterranean fruit flies, female melon flies, and

male and female oriental fruit flies (25). The roots

are used as an insecticide and vermifuge in China.

Active compounds: The major distilled oil component (80 percent) responsible for the repellency

and sterility is ß-asarone, or (Z)-2,4,5-trimethoxypropenylbenzene. Another component, asarylaldehyde

(2,4,5-trimethoxybenzaldehyde), also is repellent to

many species of insects. Both compounds are attractive to fruit flies (25). Synthesizing ß-asarone

and related compounds by a process that gives an

overall yield of 79 percent is cheaper than extracting the oil from calamus. The compounds are expected to be especially useful as fumigants for protecting stored grain from insects, as they will permeate grain-filled storage areas without leaving residues on the grain after the areas are ventilated. The

rice weevil, probably the most damaging insect pest

of stored grains, is vulnerable to ß-asarone (2).

Asarylaldehyde is available commercially.

Several other compounds obtainable from calamus oil are acoragermacrone, which is attractive

to female melon flies but is not available synthetically (25); at least eight coumarins which are potentially useful in the treatment of tuberculosis (38);

and a host of terpenes which have superior germicidal properties (49) and are used in perfumery (13).

Extraction: Raquibuddowla and Haq (43) have

published the details of a countercurrent pilot plant

method for extracting the oil from the rhizomes

with petroleum ether, which can be recovered and

reused. Three extractions of 25 kg of ground

rhizomes (1.65 mm particle size) at room temperature yield 2.71 kg of oil, from which the active compounds can be isolated by fractional distillation or

column liquid chromatography (25).

Cultivation: The plant is propagated by division.

It propagates easily in the spring or autumn and

although it thrives in moist soil, it may be grown

on dry land.

Constraints: ß-asarone has a marked depressant

effect on the central nervous system of mice, rats,

and monkeys. It reduces spontaneous locomotor activity in mice and rats, and in monkeys produces

a calming effect lasting 24 hours. The onset of action is more rapid than that of reserpine (9). Although these pharmacological properties may limit

the use of calamus oil to certain applications, they

should not prevent use of the oil for agricultural

insect control and possibly for medical purposes.

Artemisia tridentata Nutt.

Common name: Big sagebrush

Family: Asteraceae

Description: A. tridentata is a copiously branched

perennial which has short rhizomes, is aromatic,

and grows to a height of 3 m. The inflorescence is

generally dense and leafy; the flowers are fertile

and bloom from July to September. The threetoothed leaves are 2.5 cm long. The plant thrives

in light, well-drained, dry, stony soils.

Native range: Originally a native of Europe, it is

the prevailing plant of the Great American Desert,

which centers around the Salt Lake of Utah and includes portions of Utah, Colorado, northern Nevada, and northern Arizona. It is also found in the

desert areas of Washington State, in British Columbia, and in Baja, Calif.

Present and potential uses: Cattle browse this

plant on the range. The Indians sometimes use the

brittle branches for thatch. The seeds are eaten by

many kinds of birds and mammals, and California

Indians grind the seeds into a meal used for making a kind of pinole. An extract of the pollen is used

to treat hay fever.

An ethanol extract of the dry branch ends is exceptionally effective in preventing feeding on

potato leaves by the Colorado potato beetle, Leptinotarsa decemlineata Say (28). The beetle’s resistance to insecticides in potato-growing areas is an

increasingly serious problem in several areas of the

world, and this resistance probably will become

more widespread. Antifeedants could be important

in a multiple system approach (integrated pest management) to control this pest (27). In classical times,

the leaves and shoots of Artemisia species were

added to stored cereals in granaries to protect them

from weevils and other pests, and the water in

which they had been steeped was used to kill or repel insect larvae, fleas, and locusts. Several species

of ticks are killed rapidly by exposure to the vapors

of the powdered plant (19). Various parts of the

plant are used in the United States as a vermifuge,

Active compounds: Although one of the feed

ing deterrent compounds in the branches has

been identified as deacetoxymatricarin, other compounds not yet identified are also responsible for

the activity. Deacetoxymatricarin shows good antifeedant activity at a threshold of 20 micrograms/

square centimeter (μg/cm2

). An extensive series of

sesquiterpene lactones and a number of coumarins
140 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

including esculetin, scopoletin, 7-hydroxycoumarin, and 6,7-dimethoxycoumarin are present in the

plant. Strangely, although a steam distillate of A .

tridentata at 80 μg/cm2 had no effect on the feeding

activity of L. decemliniata, an aqueous extract of

the organic residue following steam distillation

showed strong activity at 5 to 10 μg/cm2 (28). Numerous species of Artemisia contain absinthin,

which is avoided by insects (15).

Extraction: The dried, ground branches are extracted with ethanol, then the extract is freed of solvent and partitioned between 70 to 90 percent aqueous methanol, chloroform, and carbon tetrachloride. Most of the deterrent activity is from the carbon tetrachloride portion, which is chromatographed on a silicic acid column eluting with successively more polar solvents (28),

Cultivation: Sagebrush has been cultivated since

1881. It can be planted at any time during October

and March in full sunlight, and grows rapidly.

Constraints: Seed germination is low—35 percent

or less. The pollen is known to cause hay fever. Deacetoxymatricarin has not been synthesized and it

is unlikely that it can be synthesized economically

for high yields because a number of inactive geometrical isomers might be formed instead. There

should be no practical problems in using crude

plant extracts for crop protection, as these can be

sprayed on crops without purification (52). A more

extensive search for insect antifeedants in sagebrush desert plants certainly is justified.

Azadirachta indica A. Juss.

Common names: Neem, nim, margosa

Family: Meliaceae

Description: The tree is of moderate to large size

(12 to 19 m tall) with a straight trunk that can attain a diameter of 1.8 m, The bark is moderately

thick; the heartwood is red, hard, and durable; and

leaves are glabrous and resemble those of marijuana. Neem bears honey-scented white flowers.

Native range: Neem commonly occurs in large

numbers in the open scrub forest in the dry zones

of India and Burma. It was introduced as an ornamental into East Africa in the last century. It is

also well established in Guinea and the Sudan (39),

Present and potential uses: Almost every part of

the neem tree is used medicinally in India. The timber is durable, is seldom attacked by termites, and

can be used for the manufacture of building materials, furniture, and other wooden objects of commercial value. In India, goatskins treated with tannins derived from the bark compare favorably with

hides processed by conventional chemicals. The

amber-colored gum exuded by the bark is used medicinally as a stimulant (53). The twigs have been

used for many years in India and Africa for general

mouth hygiene, and extracts of the bark are used

in toothpaste in Germany. Neem leaves are useful

fodder for farm animals and are reputed to have

therapeutic effects against intestinal worms and

ulcers (37).

The seed has the most commercial promise. For

centuries seed oil has been used in India for the

manufacture of a refreshing soap and has been

burned as a source of light and heat. The oil can

also be used for the manufacture of wax and lubricants. The seed cake left after oil extraction is used

as an organic manure for fertilizing cash crops of

sugarcane and vegetable gardens in India (40,41,

42). Although all parts of the tree repel insects, extracts of the seeds are outstanding repellents and

feeding deterrents for a broad spectrum of economic agricultural and household insects. Seed extracts

deter at least 25 species of crop pests in the United

States from feeding, inhibit the growth and development of others, and render others sterile (10,21,42,

48,56),

Unlike most of the present insecticides available

on the market, the seed extracts appear to be nontoxic to man and animals and are essentially nonphytotoxic. In addition, they have a systemic action when applied to some crops so that, once absorbed by the plant tissue, they offer more durable

protection to crops even after heavy rain showers.

Active compounds: Of the three proven insect

feeding inhibitors isolated from neem (meliantriol,

azadirachtin, and salannin), azadirachtin is by far

the most effective, since it can be used at concentrations as low as 0.1 part per million (ppm). Meliacin limonoids occurring in the seeds areazadirone,

azadiradione, 17-epiazadiradione, nimbin, nimbinin, gedunin, vepinin, meldenin, and nimbolin

(56). The insecticidal properties of these have not

been investigated in depth (29). The efficacy of

azadirachtin against insect pests native to the

United States (e.g., Japanese beetles, cucumber

beetles, Mexican bean beetles, Colorado potato

beetles, a number of stored product insects, aphids

and scale insects, cotton bollworms, tobacco budworms, and fall armyworms) and other countries

is discussed by Warthen (56), Schmutterer, et al.

(48), Ladd, et al. (32), Warthen, et al, (57), Redfern,

et al. (45), and Meisner, et al. (34). Salannin is also

an effective feeding deterrent for house flies (58)

and several cotton pests in Israel (34).

Extraction: Neem seed extracts that are effective

against insects have been prepared with hexane,

ethyl ether, acetone, ethanol, and methanol (21,26,
Insecticides, Insect Repel/ants, and Attractants From Arid/Semiarid-Land Plants ● 141

—

54). Although the active compounds are only slightly water soluble, Indian farmers have used water

to prepare spray solutions that prevent insect

damage to tobacco (3). A procedure has been

developed by scientists in the U.S. Department of

Agriculture (54) for isolating azadirachtin of greater

than 90 percent purity from ground neem kernels

in 0.018 percent yield. The dry kernels are extracted

first with hexane to remove largely inactive oil, then

with acetone. The extract is chromatographed on

Florisil and then by open-column liquid chromatography on Phase-bonded C-18 Hi-Flosil and

μBondapak C-18 high performance liquid chromatography.

Salannin maybe isolated from the kernels by extracting with 95 percent ethanol, partitioning the

extract between methanol and hexane, and subjecting the methanol-soluble portion to column chromatography ondiatomaceous earth followed by

chromatography on Florisil and high performance

liquid chromatography of the active eluate on

μBondapak C-18 (58).

Cultivation: Neem is a fast growing, sturdy tree

that can be established without irrigation in hot and

dry regions with annual rainfall of 500 mm or less.

It grows well on shallow, stony, or sandy soils

where agricultural crops have low yields, despite

the application of fertilizers, or fail altogether. It

thrives on dry, stony, and shallow soils with a

waterless subsoil or in places where there is a hard

calcareous or clay pan near the surface. The extensive roots of neem have the unique physiological

capacity to extract nutrients from highly leached,

sandy soils (42).

The neem tree has a wide range of possibilities

for economic development, especially in arid zone

countries. Two neem trees from Malaysia and one

from Africa are growing well in Miami, Fla., at the

USDA Horticultural Research Station and the Fairchild Tropical Garden, respectively. Neem plantations are abundant in northern Cameroon, Nigeria,

and Gambia in Africa; in India; and in Cuba, Barbados, Honduras, and Antigua. The current policy

of the U.S. Agency for International Development

(AID) is to reduce the dependence of developing

countries on imported pesticides. The U.S. Peace

Corps is encouraging the mass cultivation of neem

trees in Cameroon and Gambia. USDA has initiated

a program to develop neem as a commercial crop

in Puerto Rico and the U.S. Virgin Islands (2 I). It

is envisioned that neem could be grown effectively where other agricultural crops are unproductive

or present a severe erosion hazard.

Constraints: Although dry neem seeds are available commercially on the open market in India,

these seeds do not ordinarily germinate. Under ordinary circumstances, neem seeds do not retain

their viability for long; 2 weeks is probably the upper limit. Green (ripe) seeds, however, do germinate

well in sand and a sand-sterilized soil-cachaza mixture. Germination is improved if the inner shell is

removed before planting to expose the embryo.

Since the complicated molecular structure of azadirachtin probably precludes its synthesis, it is fortunate that practical methods are available for isolating azadirachtin.

Azadirachtin formulations used to treat growing

field crops are subject to photodegradation by

sunlight. Acetone solutions of this compound exposed for 7 days show more than a 50 percent

reduction inactivity; exposure for 16 days destroys

the compound. Present research is aimed at preventing such photodegradation (51).

Neem seed oil has an unpleasant garlic-like smell,

and the problems of deodorization, refining, and

purification in large-scale industrial production

have yet to be solved. Treating the oil with alcohol

separates most of the odoriferous fraction, which

can then be used in the manufacture of pharmaceutical preparations.

Another constraint mentioned by Radwanski and

Wickens (42) is that: “Neem cannot be grown

among agricultural crops since it will not tolerate

the presence of any other species in its immediate

vicinity and, if not controlled, may become aggressive by invading the neighboring crops. ”

The tree is tender to frost, especially in the seedling and sapling stages. In imperfectly drained soils,

growth is poor and the taproot tends to rot.

Despite these constraints, cultivation and processing of neem are promising (35). The most work

on commercial development of neem is being carried out in India by universities and government

agricultural institutes which stress applied aspects

and by USDA which is doing basic research on extraction and stabilization of the active compounds

and methods of application.

Heliopsis longipes (A. Gray) Blake

Common names: Chilcuage, peritre del pais,

chilcuan

Family: Asteraceae

Description: H. longipes is a perennial herb with

stems that are slightly woody and shrubby at the

base. It grows to 20 to 50 cm and forms new shoots
142 ● Plants: The Potentials for Extract/rig Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

each year. Its few leaves are opposite, the flowers

yellow, and the roots are slightly fleshy but fibrous.

Native range: Heliopsis grows natively in Mexico, from southern San Luis Potosi and northeastern Guanajuato and in mountainous areas south

and southeast towards Alvarez. It is found at altitudes of 1,800 to 2,100 m in areas with annual rainfall of 370 mm. Its habitat is usually the oak-forest

zone in sandy to clay soils.

Present and potential uses: Usually available in

local markets in Mexico, the dried roots are used

mainly as a spice to flavor beans and other foods.

The tongue and mouth numb and burn when minute pieces are chewed. An extract of the roots is

used for colds and pneumonia. Roots are chewed

to relieve toothache. An alcoholic extract of the

roots has been tested successfully by dentists as an

anesthetic for tooth extraction (33).

In Mexico City, a local insecticide is prepared

from Heliopsis. Some powdered root placed in the

cattle’s wounds made by warble flies kills the larvae. A petroleum ether extract of the roots is highly

toxic to house flies, adults, and larvae of Aedes mosquitoes, body lice, melonworm and southern beet

webworm larvae, bean weevils, squash bug

nymphs, German and American cockroaches, black

carpet beetles, and clothes moths (19). Spray formulations of the roots cause rapid knockdown of

flying insects.

Active compounds: The active compound in root

extracts was identified as the isobutylamide of

(E,Z,E)-2,6,8-decatrienoic acid, which has been

given the names “affinin” and “spilanthol” (23). It

has been prepared synthetically (17) but in such a

low yield that extraction is advocated for this plant.

Extraction: “Affinin” is obtained by extracting

the dried roots with petroleum ether, partitioning

the extract between this solvent and nitromethane,

and filtering the nitromethane solution through a

charcoal column. The pure compound is obtained

in 0.4 percent yield by distillation as a pale yellow

oil.

Cultivation: Wild plants have been transplanted

successfully in rows and beds at four localities in

Mexico at elevations of 1,800 to 2,400 m. The plants

were dug with picks, most of the tops cut off, and

the roots were trimmed. The rhizomes sprout readily at the nodes, so propagation by rhizome cuttings

might be successful. The plant also can be propagated commercially by seeds. Roots of suitable size

and quantity for harvest should be ready within 2

or 3 years after planting. Transplants under care

grow better than wild plants (33).

Constraints: In spite of the succulent character

of the roots, care must be used in transplanting.

When exposed to the air, the roots dry out rapidly

and shrivel within a week. Dried roots with bases

of stems attached will not grow.

“Affinin” shows a marked tendency to polymerize in the pure state, although it can be kept almost

indefinitely in solution with a hydrocarbon solvent

such as benzene or toluene at 5° C. It has a burning, paralytic effect on the tongue.

Mammoa americana L.

Common name: Mamey, mammy-apple

Family: Clusiaceae

Description: This is a handsome, conspicuous

tree 12 to 18 m tall with shiny, leathery oval leaves;

fragrant white flowers; and large globose russetbrown fruits 8 to 20 cm in diameter, with rough,

bitter skin and orange apricot-flavored pulp surrounding one to four seeds. The trunk may reach

0.9 to 1.2 m in diameter,

Native range: Mamey is indigenous to the West

Indies and tropical America.

Present and potential uses: An infusion of the edible fruits at 1 lb/gal of water is highly toxic to melon

worm larvae both as a stomach and a contact poison, and also to fleas, ticks, and lice. The powdered

seeds are very toxic to fall armyworms, melonworms, and diamondback moths, and in a water

suspension are highly toxic to the larvae of several

species of mosquitoes, American and German cockroaches, flies, ants, southern beet webworms, and

southern armyworms. The leaves have been used

for many years in Puerto Rico as a wrapping

around the stems of newly set garden plants to prevent attack by garden insects. The powdered leaves

are very effective as a stomach poison for chewing

insects. The flowers are toxic to melonworm larvae (24).

The plant is widely cultivated in the French Antilles for a liqueur (“creme de creole”) distilled from

the flowers. The fruit is usually stewed or made into

candles in Mexico. Because the wood is hard and

durable, it is useful for construction. It is also used

for cabinet making, as it is beautifully grained and

takes a high polish. The resinous gum from the bark

is used to extract chiggers from the feet. The sweet

flesh of the fruit is eaten raw or cooked, and the

juice makes a refreshing drink. The flesh normally

adheres closely to the seeds, but seedlings grown

in the Isle of Pines yield fruits in which the flesh

separates readily from the seeds.
Insecticides, Insect Repellants, and Attractants From Arid/Semiarid-Land Plants ● 743

Active compounds: The principal insecticidal

constituent, “mammein” or “mameyin,” which

comprises 0.19 percent of the seed weight, has been

identified as 4-n-propyl-5,7-dihydroxy-6-isopentenyl-8-isovalerylcoumarin. The related compound

4-phenyl-5,7-dihydroxy-8-isopentenyl-6-isovalerylcoumarin, isolated from the fruit pulp, is also toxic to insects. An additional 24 coumarins isolated

from the fruits are not insecticidal. All the coumarins are effective uncouplers of oxidative phosphorylation (8,24).

Extraction: Mammein is isolated by percolating

the ground, large (40 g), egg-shaped seeds or fruits

with petroleum ether, removing the solvent, dissolving the residue in acetone, and chromatographing on a column of alumina. The yield is about 180

g of mammein from 100 kg of seed.

Cultivation: The tree is cultivated for the edible

fruit on Caribbean islands, and in Mexico, Central

America, and South America. Several trees are

growing at the Fairchild Gardens in Miami, It can

be grown in Florida as far north as Palm Beach, but

never has been grown successfully in California,

probably because it will not stand more than 2 to

3 degrees of frost. The seeds germinate readily if

planted in light, sandy, loam soil, and seedlings

usually bear at 6 to 8 years of age. The tree is propagated by seeds and also by inarching and budding.

The fruit ripens in summer.

Constraints: Although no serious attempt has

been made at export or commercial use, there

should be no difficulty in making this a commercial crop in southern Florida, Puerto Rico, or the

Virgin Islands.

Ocimum basilicum L.

Common names: Basil, sweet basil, garden basil

Family: Lamiaceae

Description: Sweet basil is an aromatic plant

reaching a height of 60 to 70 cm. It is a glabrous

or slightly pubescent herb with petiolate leaves and

white or slightly purplish flowers.

Native range: O. basilicum is indigenous to

France, Italy, Spain, Germany, Haiti, Indonesia,

Samoa, Africa, India, Pakistan, and the Philippines.

Present and potential uses: Essential oil distilled

from the fresh flowers or the entire basil plant is

employed extensively as a flavor in confectionery,

baked goods, condiments, and spiced meats and as

an aroma in certain perfume compounds. It has antipyretic, antiseptic, diaphoretic, diuretic, and

stimulant properties and, therefore, has been recommended for gastric disorders, malarial fevers,

and skin diseases. The oil is an excellent repellent

and larvicide for almost all species of mosquitoes

and for mites and aphids (7,44). In India, freshly

collected leaves or their ether or acetone extracts

are rubbed on the back and arms to effectively repel

mosquitoes for 4 to 6 hours. The essential oil is a

powerful attractant for male fruit flies, Dacus correctus. Topical application of the oil inhibits growth

and development of milkweed bugs, Oncopeltus

fasciatus (6), The oil also has fungicidal properties.

Active compounds: Although not all of the repellent compounds in the essential oil have been identified, cineole, linalool, and methyl chavicol—which

account for 3 percent, >50 percent, and 33 percent

of the oil, respectively—are implicated (14). The

fruit fly attractant has been identified as methyl

eugenol. Two compounds, designated as “juvocimene I“ and “juvocimene I I,” are responsible for

the juvenilizing effects,

Extraction: The oil is extracted by steam distillation or enfleurage of the leaves or leaves and flowers. The yield depends upon soil fertility and seasonal conditions; cloudy or rainy weather immediately preceding the harvest reduces the yield,

whereas bright sunny weather increases it. The

highest oil yield obtained from any location was 49

kg/ha. Extraction of the leaves and/or flowers with

solvents such as ether or acetone also produces oil

that is repellent or toxic to insects. Since the many

active components can be obtained readily from

basil oil, their synthesis would be much less practical commercially.

Cultivation: The former Division of Drug and

Related Plants of USDA experimentally cultivated

the plant in Virginia for several years during the

1930’s. The seed was imported from France and the

whole fresh flowering herb was used for distillation of the oil. The plants grew rapidly on clay soil

improved by mulching with pulverized stable

manure. A highly fertile soil produces large succulent plants with low oil content.

Constraints: The seed will not germinate if

planted at a depth of more than 0.6 cm. The cultivation of this annual in the United States should present no unusual difficulties. Since the crop is grown

easily and good yields are obtained, the oil could

be produced in many localities of the United States

at reasonable prices (l).

Tagetes minuta L .

(synonym: T. glandulifera Schrank)

Common names: Mexican marigold, stinking

roger

Family: Asteraceae

Description: The plant is a glabrous branched annual attaining a height of 0.9 m or more and possessing clusters of fragrant orange-yellow flowers
144 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

opening in August. It grows in any well-cultivated

site, even in poor, rather dry soils.

Native range: T. minuta is native to Central and

South America, especially Chile, but grows widely

in Ethiopia, Kenya, and other areas of East Africa

(especially in the highland areas) and northern India. It has been naturalized in the Eastern United

States and South Africa, and occurs wild in sandy

waste places of the Coastal Plain in North Carolina

and in Spain.

Present and potential uses: The oil produced by

the plant’s seeds, leaves, and flowers is strongly repellent to blowflies and is useful in the tropics as

a blowfly dressing. A dressing for sheep infested

with blowfly larvae consists of an emulsion of 20

percent carbon tetrachloride, 5 percent Tagetes oil,

6 percent wool grease, and water. The emulsion

breaks down soon after application, the larvae are

killed within 1 minute, and the carbon tetrachloride and water soon evaporate. The leaves are used

locally in Africa and India to repel mosquitoes and

safari ants and recently have been found to kill mosquito larvae. The oil is more toxic to the larvae than

DDT (4,36). The oil prevents molting, thus causing

juvenilization in Dysdercus kcoenigii (46). It also

possesses significant antitumor activity against the

Lewis lung carcinoma in vivo (16). The oil possesses

tranquilizing, hypotensive, bronchiodilatory, spasmolytic, and anti-inflammatory properties. Tagetes

roots possess fungicidal and nematocidal properties (46).

Active compounds: Two of the mosquito larvicidal components of the oil have been identified as

(E)-5-ocimenone (2,6-dimethyl-2,5,7-octatrien-4-one)

(36) and the organic sulfur polyacetylenic compound a-terthienyl. The latter is also responsible for

the nematocidal and bactericidal properties of the

plant (4). The compound possessing juvenilizing

properties has been identified as tagetone (2,6-

dimethyl-5,7-octadien-4-one), which comprises 50

to 60 percent of the oil. These compounds have

been synthesized. The oil also contains numerous

organic sulfur-containing acetylenes, flavonoids,

and carotenoids in addition to the terpenes ocimene, limonene, and estragole, which are used in

perfumes and flavoring. The Japanese essential oil

(“Ho-leaf oil”) also contains tagetonol (2,6-dimethyl-7 -octen-6-ol-4-one), which has been synthesized (55).

Extraction: The ground fresh leaves and flowers

or other aerial portions are steam distilled, the

distillate is extracted with hexane or petroleum

ether, and the solution is dried. Evaporation of the

solvent yields 0.5 to 1.0 percent of the yellow essential oil.

Cultivation: The seeds should be planted in late

May in open, sunny sites. They germinate rapidly.

Constraints: Although several of the pesticidal

components of Tagetes oil have been prepared synthetically in the laboratory, the synthetic methods

involve multistep processes, which sometimes do

not give the desired geometric isomers, and yields

are poor. However, large-scale cultivation of the

plant should pose no insurmountable difficulties,

and the oil, which is easily obtained by distillation,

can be used for pest control and as a source of pesticidal and medicinal compounds.

Although all of the seven plants discussed in this

report are potential candidates for crop development and commercialization, the neem tree is by

far the most likely to succeed despite the constraints mentioned. As a broad spectrum pesticide,

neem is unsurpassed among the known insecticidal

botanical, both in the number of pest insects affected and the extremely small amounts required

to reduce crop damage and cut down on the

amounts of synthetic insecticides necessary. The

leaves repel insects; the twigs are used as antiseptic toothbrushes; the seed oil is used for illumination and soapmaking; formulations of the seeds

have powerful insect repellent, toxicant, feeding

deterrent, and growth inhibiting properties; the oilfree seeds make an excellent fertilizer; and the

timber, which is resistant to termites, is useful for

home and furniture building. Furthermore, both the

leaves and seeds contain compounds with considerable medicinal activity. Neem extracts, as well as

azadirachtin and salannin, have no apparent mammalian toxicity, are not mutagenic, and are not

phytotoxic at the concentrations normally used to

control insects. The systemic properties of neem

formulations are a definite advantage.

The neem tree begins to bear fruit in its fifth year

and may live for over 250 years. It is easy to grow

and requires virtually no extra care by the farmer.

One tree produces 30 to 50 kg of seeds per year.

Thirty kg of seeds yield 6 kg of neem oil and 24 kg

of neem cake. The market price for neem oil in India is approximately $1 per kg and for neem cake

is less than 50 cents per kg. Over 14 million neem

trees exist in India alone (47). Neem is a prime candidate for the establishment of cottage industries

in India and East Africa. Neem trees grow abun-
Insecticides, Insect Repel/ants, and Attractants From Arid/Semiarid-Land Plants ● 145 —

dantly in large areas of Asia, Africa, and the Caribbean. At the USDA Horticultural Research Station

in Miami, several of the trees are thriving and

l-year-old seedlings obtained from pollination are

already 1.5 m tall. Two-year-old neem trees are

growing at the Escuela Nacional de Ciencias Forestalls in Comaqua, Honduras. It is recommended

that these efforts to develop neem as a commercial

crop in the United States and Central and South

America be assigned a high priority, implemented,

and expanded as rapidly as possible.

1. Anonymous, Drug and Condiment Plants, U.S. Department of Agriculture Handbook No. 172 (Washington, D. C.: U.S. Government Printing Office, 1960),

Pp. 6-7.

2. Anonymous, “~-Asarone is Effective Insect Chemisterilant, ” Chemical and Engineering News, Apr. 16,

1979, p. 24.

3. Anonymous, “Lab to Land, Good News to the Tobacco Growers, ” Central Tobacco Research Institute

Leaflet, Rajahmundry, India, 1979.

4. Arnason, T., Swan, T., Wat, C. K., Graham, E. A., Partington, S., and Towers, G. H, N., “Mosquito Larvicidal Activity of Polyacetylenes From Species in the

Asteraceae,” Biochemical Systematic and Ecology

9:63-68, 1981.

5. Ayensu, E. S., “Plants for Medicinal Uses With Special Reference to Arid Zones, ” Arid Land Plant Resources, J. R. Goodin and D. K. Worthington (eds.]

(Washington, D. C.: Smithsonian Institution, 1979), pp.

117-178.

6. Bowers, W. S., and Nishida, R., “Juvocimenes: Potent Juvenile Hormone Mimics From Sweet Basil, ”

Science 209:1030-1032, 1980,

7. Chavan, S. R., and Nikam, S. T., “Mosquito Larvicidal

Activity of Ocimum basilicum Linn., ” Indian Journal of Medical Research 75:220-222, 1982.

8. Crombie, L., Games, D. E,, Haskins, N. J., and Reed,

G. F., “Extractives of Mammea americana L., Part V,

The Insecticidal Compounds, ” Journal of the Chemical Society, Perkin Transactions I: 2255-2260, 1972.

9. Dandiya, P. C., and Bapna, J. B., “Pharmacological

Research in India,” Annual Review of Pharmacology,

No. 14, 1974, pp. 116-117.

10. Doria, J. J., “Neem: The Tree Insects Hate, ” Garden

Magazine, No. 4 (July-August): 8-11, 1981.

11, Feeny, P., “Plant Apparency and Chemical Defense,”

Biochemical Interaction Between Plants and Insects,

J, W. Wallace and R. L, Mansell (eds,) (New York:

Plenum Press, 1976), pp. 1-40,

12. Finch, S., “Chemical Attraction of Plant-Feeding Insects to Plants, ” Annals of Applied Entomology

5:67-143, 1980.

13. Fujita, S., Enomoto, Y., Suemitsu, R., and Fujita, Y.,

“Miscellaneous Contributions to the Essential Oils of

the Plants From Various Territories, XXVIII: On the

Components of the Essential Oils of Acorus calamus

Linn. var. angustatus Bess.,” Yakugaku Zasshi 91:571-

574, 1971.

14. Guenther, E., The Essential Oils (New York: Van

Nostrand, vol. III, 1949) (“Individual Essential Oils

of the Plant Families Rutaceae and Labiatae”), pp.

399-415,

15. Heywood, V. H., Harbourne, J. B., and Turner, B. L.

(eds.), The Biology and Chemistry of the Composite,

London, vol. I, 1977, p. 427.

16. Ickes, G. R., Fong, H. H. S., Schiff, P. L., Jr., Perdue,

R. E,, Jr,, and Farnsworth, N. R., “Antitumor Activity and Preliminary Phytochemical Examination of

Tagetes minuta (Compositae),” Jourmd of Pharmaceutical] Sciences 62:1009-1011, 1973.

17. Jacobson, M., “Constituents of He2iopsis Species, IV:

The Total Synthesis of Trans Affinin, ” Journal of the

American Chemical Society 77:2461-2463, 1955.

18. Jacobson, M., Insecticides From Plants: A Review of

the Literature, 1941-1953 (Washington, D. C.: U. S.

Government Printing Office, 1958), p. 24.

19. Jacobson, M., Insecticides From Plants: A Review of

the Literature, 1954-1971 (Washington, D. C.: U.S.

Government Printing Office, 1975), pp. 8-9.

20. Jacobson, M., “Isolation and Identification of Insect

Antifeedants and Growth Inhibitors From Plants: An

Overview,” Proceedings, Zst International Neem Conference, Rottach-Egern, June 16-18, 1980, 1981, pp.

13-19.

21. Jacobson, M., “Neem Research in the U.S. Department of Agriculture: Chemical, Biological and Cultural Aspects, ” Proceedings, 1st International Neem

Conference, Rottach-Egern, Germany, June 16-18,

1980, 1981, pp. 33-42.

22. Jacobson, M., “Plants, Insects, and Man—Their Interrelationships,” Economic Botany 36:346-354, 1982.

23. Jacobson, M., Acree, F., Jr., and Hailer, H. L., “Correction of the Source of “Affinin” (N-Isobuty l-2,6,8-

decatrienamide),” Journal of Organic Chemistry 12:

731-732, 1947.

24. Jacobson, M., and Crosby, D. G. (eds.), Naturally Occurring Insecticides (New York: Dekker, 1971),

25. Jacobson, M., Keiser, I., Miyashita, D. H., and Harris, E. J., “Indian Calamus Root Oil: Attractiveness

of the Constituents to Oriental Fruit Flies, Melon

Flies, and Mediterranean Fruit Flies, ” Uoydia 39:

412-415, 1976.

26, Jacobson, M., Reed, D. K., Crystal, M. M., Moreno,

D. S., and Soderstrom, E. L., “Chemistry and Biological Activity of Insect Feeding Deterrents From Certain Weed and Crop Plants, ” Entomologia Experimentalis et Applicata 24:448-457, 1978.

27, Jermy, T., “Biological Background and Outlook of the

Antifeedant Approach to Insect Control,” Acta Phytopathologica of the Academy of Sciences of Hungary

6:253-260, 1971.
146 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

28. Jermy, T., Butt, B. A., McDonough, L., Dreyer, D, L.,

and Rose, A. F., “Antifeedants for the Colorado Potato

Beetle. I: Antifeeding Constituents of Some Plants

From the Sagebrush Community,” Insect Science Application 1:237-242, 1981.

29. Kraus, W., Cramer, R., Bokel, M., and Sawitzki, G.,

“New Insect Antifeedants From Azadirachta indica

and Melia azedarach, ” Proceedings, Ist International

Neem Conference, Rottach-Egern, Germany, June

16-18, 1980, 1981, pp. 53-62.

30. Kubo, L, “Pharmacies in the Jungle,” Wor)d Book Science Annual, 1982, pp. 126-137.

31. Kubo, 1., and Nakanishi, K., “Some Terpenoid Insect

Antifeedants From Tropical Plants, ” Advances in

Pesticide Science, H. Geissbuhler (cd.), pt. 2 (New

York: Pergamon Press, 1979), pp. 284-294.

32. Ladd, T. L., Jr,, Jacobson, M., and Buriff, C. R., “Japanese Beetles: Extracts From Neem Tree Seeds as

Feeding Deterrents, ” Journal of Economic Entomology 71:810-813, 1978.

33. Little, E. L., Jr., “Heliopsis longipes, a Mexican Insecticidal Plant Species, ” Journal of the Washington

Academy of Sciences 38:269-274, 1948.

34. Meisner, J., Ascher, K. R. S., Aly, R., and Warthen,

J. D., Jr., “Response of Spodoptera littorals (Boisd.)

and Earias insulana (Boisd. ) Larvae to Azadirachtin

and Salannin, ” Phytoparasitica 9:27-32, 1981,

35. Michel-Kim, H., and Brandt, A., “The Cultivation of

Neem and Processing It in a Small Village Plant,” Proceedings, Ist International Neem Conference, Rottach-Egern, Germany, June 16-18, 1980, 1981, pp.

279-290.

36. Maradufu, A., Lubega, R., and Dorn, F., “Isolation

of (5 E)-Ocimenone, a Mosquito Larvicide From

Tagetes minuta, ” Lloydia 41:181-183, 1978.

37. Okpanyi, S. N., and Ezeukwu, G. C,, “Anti-inflammatory and Antipyretic Activities of Azadirachta indica, ” Planta Medica 41:34-39, 1981.

38. Patra, A., and Mitra, A. K,, “Constituents of Acorus

calamus Linn., ” Indian Journal of Chemistry 17B:

412-414, 1979.

39. Radwanski, S. A., “Neem Tree. 1: Commercial Potential, Characteristics and Distribution, ” World Crops

and Livestock 29:62-66, 1977,

40, Radwanski, S. A., “Neem Tree. 2: Uses and Potential Uses, ” World Crops and Livestock 29:111-113,

1977.

41. Radwanski, S. A., “Neem Tree. 3: Further Uses and

Potential Uses,” World Crops and Livestock 29:167-

168, 1977.

42. Radwanski, S. A., and Wickens, G. E., “Vegetative

Fallows and Potential Value of the Neem Tree (Azadirachta indica~ in the Tropics,” Economic Botany

35:398-414, 1981.

43. Raquibuddowla, M., and Haq, A., “Pilot Plant Extraction of Oil From Acorus calamus Linn.,” Bangladesh

Journal of Scientific and Industrial Research 9:161-

166, 1974.

44. Rathore, H. S,, “Preliminary Observations on the

Mosquito Repellent Efficacy of the Leaf Extract of

Ocimum sanctum, ” Pakistan Journal of Zoology

10:303, 1978,

45. Redfern, R, E., Warthen, J. D., Jr,, Mills, G. D., and

46

47,

48,

49,

504

51,

52.

53.

54.

55,

56.

57.

58.

Uebel, E. C., “Molting Inhibitory Effects of Azadirachtin on Large Milkweed Bugs, ” Agricultural Research Results, ARR-NE-5, USDA, Beltsville, Md.,

1979,

Saxena, B. P., and Srivastava, J. B., “Tagetes minuta

L. Oil—A New Source of Juvenile Hormone Mimicking Substance, ” Indian Journal of Experimental Biology 11:56-58, 1973.

Saxena, R. C., International Rice Research Institute,

personal communication, 1982,

Schmutterer, H., Ascher, K. R. S., and Rembold, H.

(eds.), “Natural Pesticides From the Neem Tree (Azadirachta indica A. Juss.), Proceedings, Ist international Neem Conference, Rottach-Egern, Germany,

June 16-18, 1980, 1981.

Shah, S. C., and Gupta, L. K., “Note on Pharmacognostic Study of the Rhizome of Acorus calamus

Linn,, ” Indian Journal of Agricultural Research 11:

113-115, 1977.

Smith, A. E., and Secoy, D. M. “Plants Used for Agricultural Pest Control in Western Europe Before

1850, ” Chemistry and Industry 1981:12-17, 1981.

Stokes, J. B,, and Redfern, R. E. “Effect of Sunlight

on Azadirachtin: Antifeeding Potency, ” Journal of

Environmental Science and Health A17:57 -65, 1982.

Sutherland, 0, R, W., “Invertebrate-Plant Relationships and Breeding Pest-Resistant Plants, ” Proceedings, Znd Australasian Conference on Grassland Invertebrate Ecology (Wellington, New Zealand: Government Printer, 1980), pp. 84-88.

Thompson, E. B,, and Anderson, C. C., “Cardiovascular Effects of Azadirachta indica Extract, ” Journal

of Pharmaceutical Sciences 67:1476-1478, 1978,

Uebel, E. C., Warthen, J. D., Jr., and Jacobson, M.,

“Preparative Reversed-Phase Liquid Chromatographic Isolation of Azadirachtin From Neem Kernels, ”

Journal of Liquid Chromatography 2:875-882, 1979.

Vig, O. P., Ram, B., and Vig, B. “Terpenoid Part

LXVII. Synthesis of dl-Tagetonol, ” Journal of the Indian Chemical Society 50:408-409, 1973,

Warthen, J. D., Jr., “Azadirachta indica; A Source of

Insect Feeding Inhibitors and Growth Regulators, ”

Agricultural Reviews and Manuals, ARM-NE-4,

USDA, Beltsville, Md., 1979,

Warthen, J. D., Jr., Redfern, R. E., Uebel, E. C,, and

Mills, G. O., Jr,, “An Antifeedant for Fall Armyworm

Larvae From Neem Seeds,” Agricultural Research Results, ARR-NE-1, USDA, Beltsville, Md,, 1978.

Warthen, J. D,, Jr., Uebel, E. C., Dutky, S. R., Lusby,

W. R., and Finegold, H., “Adult House Fly Feeding

Deterrent From Neem Seeds,” Agricultural Research

Results, ARR-NE-2, USDA, Beltsville, Md., 1978.
MARINE PLANTS: A UNIQUE AND UNEXPLORED RESOURCE*

William Fenical

Instituete of Marine Resources

Scripps Institution of Oceanography

University of California, San Diego

The seas provided a suitable site for the early evolution of all life. Ever since plants and animals

developed structures and mechanisms that enabled

them to survive on land, terrestrial and aquatic

plants have been exposed to different abiotic and

biotic selective pressures. Marine plants, which,

unlike terrestrial plants, have evolved and adapted

to life in a largely stable but saline environment,

have developed many unique chemical structures

not found in terrestrial plants.

The photosynthetic plants in the sea represent the

foundation of the marine food web. The oceans occupy 70 percent of the Earth’s surface, and the

marine plants are known to provide at least the

same percentage of available oxygen through photosynthesis. Marine plants are represented both by

seaweeds, macroscopic forms largely inhabiting the

shallow-water coastal zones, and by phytoplankton,

free floating, widely distributed unicellular marine

plants. Although a few flowering plants (angiosperms) are abundant in shallow waters, the majority of marine plants are algae, typified by their

lack of a vascular system which serves for nutrient

transport. Although all are classified as algae, these

plants have an amazing taxonomic diversity. Marine algae have been subdivided into at least 12

distinct phyla (16):

Macroscopic forms

Rhodophyta . . . the

Phaeophyta . . . the

Chlorophyta . . . the

Cyanophyta . . . the

Chrysophyte . . . . the

Haptophyta . . . . *

Xanthophyta . . . . *

Microscopic,

red seaweeds

brown seaweeds

green seaweeds

blue-green algae

yellow-green algae

usually unicellular forms

Bacillariophyta. . the diatoms

Prasinophyta . . . *

Eugenophyta . . the green algae

Cryptophyta . . . *

Dinopbyta . . . the dinoflagellates

● No common nomenclature exists for these algal phyla

Because of the highly unique and specific colorations of these groups, the analysis of numerous

● Another paper on marine plant products was written for the OTA

workshop by Ara der Marderosian of the Philadelphia College of Pharmacy and Science. Dr. der Marderosian’s paper focused on the early

stages of marine pharmaceutical development in the late 1960’s and

mid-1970’s. The constraints that existed then in this field still are present today—namely, problems of procuring and screening plants and exphotosynthetic pigments has become a fundamental feature of algal classification. While no precise

estimate is possible, well over 100,000 species of

marine algae are thought to exist in various marine

habitats.

Biogeographically, marine algae live in all parts

of the ocean, from the tropics to the poles. Seaweeds and the phytoplankton frequently are found

in extremely high concentrations. Although precise

figures are difficult to substantiate, the primary productivity of 1 acre of open, plankton-rich ocean

may be twice as large as that of a Midwest corn

field.

A Unique Chemical Resource

Marine plants have evolved unique and highly

specialized biochemical pathways to adapt to their

unique seawater medium and survival pressures (7).

The marine environment is rich in halogens, mainly in the form of chloride and bromide salts. Other

chemical entities, such as sulfate, are also found in

high concentrations. Marine plants use these elements in biosynthetic processes to produce compounds such as halogenated terpenes, acetogenins

and alkaloids which are unique to the marine environment (6).

Many marine plants have evolved toxins and deterrents to enhance their survival in the face of

abundant and freely migrating predators. Even

though the same evolutionary pressures have produced similar responses in terrestrial plants, the

defensive chemicals from marine plants are novel

and represent interesting new chemical species

which are unprecedented in terrestrial sources,

even in closely related terrestrial algae.

Other adaptations, such as the development of

resistance to wave shock and motion, have resulted

in the synthesis of complex polysaccharides (complex sugars) which act to reduce the surface tension of seawater. These constituents, too, are highly

specific to marine algae and help illustrate the

unique genetic compositions of marine plants in

general.

tracting, isolating and characterizing their active ingredients; lack of both

an adequate number of trained personnel and a multidisciplinary approach; and inadequate patent protection. Dr. der Marderosian advocates

increased collaboration between government and industry and more longterm support for marine plant products work.

147
148 . p/ants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals— workshop Proceedings

History of the Early Use

of Marine Algae

Many societies, particularly those in the IndoPacific region and Asia, have developed important

uses for marine algae (2). The most significant example is the use of various benthic seaweeds, such

as Porphyra spp. and Laminaria spp,, as food or

food supplements. Such delicacy items as “Nori,”

and “Wakami” have become integral features of

most diets in Japan. Shortages of these seaweed

products have spawned intense aquiculture activities; for example, well over 18,000 MT of “Nori”

are produced each year. A unicellular phytoplankton is harvested in several coastal regions in Thailand and used as the basis of a thick fish broth. The

algae generally are not considered highly nutritious

foods, but provide a broad base of mineral nutrition and roughage in the diet, and perhaps are most

important for flavoring fish and rice dishes.

The classical use of marine algae as animal fodder and soil manure in northwest Europe has withstood the test of time. Marine algae, particularly

that stranded on the beach after a storm, is collected

and fed directly or after drying to sheep and cattle

or applied on fields at rates of 56 to 67 MT/ha (25

to 30 tons/ac) as manure. This green manuring has

been particularly useful on potato fields in the

British Isles.

As man has become more aware of the unique

chemical composition of marine algae, numerous

additional products have been developed. A classical use for seaweeds has been the extraction of

halogens and potash. Brown algae were used for

several decades as the major source of iodine, and

the red seaweeds were used on a few occasions for

the derivation of bromine. The Pacific coast of

America between 1910 and 1930 was the site of a

flourishing potash industry based on the high potassium concentrations found in local brown algae.

It is not surprising that a wide variety of lesser

known uses of marine algae also evolved. Numerous species of marine algae are used in China as

herbal medicines to treat many maladies, ranging

from intestinal problems to sunstroke, In addition,

the gelling properties of aqueous extracts of numerous algae have been used in a host of food-related

applications,

Modern Use of Marine Algae

The classical uses of marine algae as sources for

elemental halogens, potash, and crude food thickeners largely were curtailed by the mid-1900’s as

other, more cost-efficient sources were developed.

But also during this period, many currently used

algal products, particularly algal polysaccharides,

became established. A well-established industry in

the United States now harvests marine algae (seaweeds) and extracts agar, carrageenan, and alginate. Agar is a sulfated polysaccharide (a polymer

of the simple sugar galactose) found in many species of the red algae Gelidium, Gracilaria, a n d

Pterocladia. This product is used mainly in the

specialty food industry as a gelling agent and thickener, but also is used, among other things, as a biochemical adsorbent and as a culture and nutrient

medium for bacteriological research, Agar is also

a major nutrient medium for the industrial production of antibiotics.

Another specialty polysaccharide, carrageenan,

is extracted routinely from red algae of the general

Chondrus, Gigartina, and Eucheuma. This product

also is a polymer of the simple sugar galactose, and

its major applications resemble those of agar but

are more widespread within the food industry. A

complete description of the diverse applications of

agar and carrageenan are given by Chapman (2).

Polysaccharides derived from red algae support

worldwide industries that produce about 18,000

MT per year at a total market value of about $200

million.

The brown seaweeds are also prized for their

polysaccharide components, particularly alginate,

Alginate is a mixed mannuronic and guluronic acid

polymer comprising 20 to 30 percent of the overall

composition of numerous brown seaweeds (particularly the so-called “kelps”), This polysaccharide

represents a major worldwide industrial product

generally prized for its thickening properties (e.g.,

in paints), emulsion stabilization properties, and

gelling characteristics, Agar and carrageenan are

far superior to alginate for use in foods, but alginates are particularly valuable for incorporation

into industrial products and processes,

Even though the majority of the products derived

from marine algae come from the readily collected

macroscopic forms, several products are being produced by the culture of unicellular forms. The green

alga Dunaliella, for example, recently has been

established in mass culture as a commercial source

for glycerol (glycerine) and the orange pigment

beta-carotene. Glycerol is used industrially for

numerous purposes, including in the manufacture

of solvents, sweeteners, printing ink, antifreeze,

shock absorber fluid, etc. Leffingwell and Lesser

(12) have cited 1,583 different uses for glycerol, including the production of dynamite. Beta-carotene,

the precursor to vitamin A, is used to impart color
Marine Plants: A Unique and Unexplored Resource ● 149

and provide vitamin A in animal feeds and human

foods such as margarine, It is also used as a

sunscreen agent.

Several algal species have been used consistently in the biomedical sciences. In particular, the red

algae Digenia simplex and various Chondria species have been exploited in Asia for their content

of effective anthelmintic drugs (to control intestinal

parasites). The seaweeds’ active components, kainic acid and domoic acid, were found to be relatives

of simple amino acids, and they now are extracted,

purified, and marketed as drugs in Asia. No other

examples of successfully algae-derived pharmaceuticals exist, but there certainly is a great potential

for further development in this area.

Development of Marine Algal

The potential for developing a wide variety of

commercial products from marine algae is great.

As the supply of fossil fuels decreases, it will be

essential to replace them with living or renewable

resources. Even though relatively little basic

chemical research has been performed on marine

algae, it now seems clear that mass culture techniques, both in the ocean itself and in controlled

coastal facilities, have great potential to provide industrially significant quantities of marine algae. As

a result of funding from the Department of Energy

(DOE) through the Solar Energy Research Institute

(SERI) and several other agencies, scientists are

learning of the nutrient and light requirements for

effective algal growth. Marine algae probably will

be a focus of considerable attention over the next

decade as we investigate new resources for both

energy and industrial product development.

Although relatively few algal products have been

developed successfully by industry, the potential

for the discovery and development of a plethora of

unique new products seems unlimited. A few of the

most notable areas for exploitation in the near future are summarized below.

Marine Algae for Biomass Conversion

Work already has begun to assess marine and

other euryhaline algae as basic resources for

biomass, with the expectation that through fermentation biomass can be converted easily to methane

gas, ethanol, and other useful chemicals. A major

concern is discovering plant sources that are easily grown in relation to their nutrient requirements,

are highly efficient photosynthetically, and will

yield readily digestible organic matter. At least the

majority of these criteria are met by numerous species of macroscopic and microscopic algae. Algae

are efficient photosynthetically and are cultured

conveniently in the open ocean, ponds, or controlled (hemostatic) culture vessels. A major problem in algal biomass conversion lies in effective fertilization of cultured seaweeds and in cost-efficient

harvesting of unicellular algae, Biomass conversion

processes of any type are not cost efficient within

the current economic structure. However, technology should continue to be developed so that resources and knowledge will be available for implementation when needed at a future date.

Pharmaceutical Development

The history and development of the modern pharmaceutical industry are based upon the extraction

of biologically active substances from terrestrial

plants and microorganisms. As human diseases

change and pathogenic bacteria become resistant

to established antibiotics, it becomes exceedingly

important that new pharmaceuticals are available

to reduce human suffering. As mentioned earlier,

kainic acid, an anthelmintic drug in the Orient, was

the first example of a useful drug extracted from

marine algae (14), Few complete biomedical investigations have been performed on marine algae.

Historically, biomedical applications of alginates

and other algal polysaccharides have been clearly

emphasized. This subject has been reviewed recently in an edited volume entitled “Marine Algae in

Pharmaceutical Science, ” by Hoppe, Levring, and

Tanaka (10). Although numerous uses for algal

polysaccharides have been established, the majority

of applications involve use of their physical properties rather than their physiological activities, A surprising percentage of algal polysaccharides, however, show antiviral activity, This area of drug

development is of current interest. Extracts of red

seaweeds from the family Dumontaceae, particularly the extract of Constantine simplex, contain a

specific and potent antiviral substance against

Herpes simplex virus (4). The incidence of disease

in the United States attributed to H. simplex h a s

reached epidemic proportions,

The macroscopic seaweeds (red, brown, green,

and blue-green algae) all possess structurally

unusual, biologically active metabolizes. Compounds that show impressive antibiotic activities

(5,18), and a number of unique metabolizes that

show impressive cytotoxicities have been isolated

from algae (9). The brown algal metabolite stypol-
150 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

dione (from Stypopodium zonale), for example, is

a potent cancer cell cytotoxin which operates

through a novel mechanism (11), Few comprehensive studies of microscopic algae have been reported, but there are several reports of antimicrobial activities (1,3). In addition, numerous phytoplankton species, such as Gymnodinium breve,

Gonyaulax catanella, Gonyaulax tamarensis, Prymnesium parvum, inter alia, are known to produce

the powerful toxins brevetoxin-B (13), saxitoxin

(17), and prymnesin (15). In general, however, almost no information exists on the pharmacological

potentials of the tens of thousands of microscopic

plant species in the sea. This is due mainly to the

difficulty in purifying a single species of unicellular

algae and growing it for biomedical studies. This

author is convinced that much could be learned

from just such a dedicated effort.

Although a single algae-derived product exists,

the slow rate of developing new marine pharmaceuticals clearly can be linked to the limited involvement of the major pharmaceutical companies.

U.S. companies do not have a well-defined “entry”

into this exploitation, and their lack of confidence

is self-perpetuating within industry. Unlike any activity these industries have undertaken, marine explorations involve marine biological and oceanographic expertise, and the proper interface for this

education has not existed. In addition, marine biological laboratories in the past have not employed

scientists possessing capabilities in biomedical

areas. The tide is changing, however, and major

programs have developed under the auspices and

support of the Department of Commerce’s Sea

Grant Program. The Sea Grant effort in biomedical

development is a perfect blend of academic and industrial (basic and applied) research that is yielding

fruitful results. The Sea Grant project, “Marine

Chemistry and Pharmacology Program,” at the University of California, for example, has discovered

over 75 pure compounds with potential biomedical

use and they have emphasized a collaborative effort with the pharmaceutical industry. This latter

collaboration is the vital link to ensure that basic

marine research finds its way to the industry that

is capable and interested in developing new products.

Other governmental agencies have been involved

to a more limited extent in marine biomedical development. For example, the National Cancer Institute has dedicated significant resources toward

the isolation of new antitumor drugs. Here again,

the need to involve basic marine scientists to locate,

identify, and quantitate suitable marine species for

study was underemphasized, and considerable difficulties (which affected output) were encountered,

The prospect for future development in this area

is heavily underscored by the unique nature of

marine-derived natural products. Based upon current chemical studies, it is clear that a wealth of

novel structures exists in marine plants, and future

biomedical studies of these compounds should

prove highly productive.

The use of naturally occurring compounds to

control pests forms the basis of the agrichemical

industry. For example, pyrethrins, insecticidal

components isolated from pyrethrum, a daisy-like

flower of the chrysanthemum family, and their synthetic derivatives continue to dominate agrichemical use. Many synthetic pesticides are halogenated

compounds. Since halogenation is a natural process

in marine plants, the compounds produced are likely to possess agrichemical activity, Only a few studies have been completed, but initial collaborative

investigations indicate considerable promise. Of

twelve purified algal metabolizes thoroughly assessed in herbicidal and insecticidal bioassays, nine

showed some activity, and one was nearly equivalent to DDT in insecticide activity (8).

Here again, the success in developing marine algal agrichemicals lies in developing a close relationship between academic and industrial research. A

limitation on commercial development of marine

extracts is that little government funding is available outside of the U.S. Department of Agriculture.

Agricultural research funding should be expanded

in the United States to include a greater component

of academic research.

Food and Food Products

In addition to providing agar, carrageenan, and

alginate, marine algae are recognized sources of

triglycerides (many species are up to 20 percent

triglycerides) which are used as cooking oils, and

of numerous useful food products, such as hexose

sugars and amino acids. Although seaweeds usually are low in protein, many phytoplankton are

rich protein resources. Exploitation of protein-rich

blue-green algae already has begun through the increased interest in Spirulina as a health food.

Spirulina clearly is not the only algal species to

qualify as a suitable food, and particularly the bluegreen algae (many of which are nitrogen fixing)
-

hold great promise for providing new protein resources. The American Medical Association emphasizes that good cardiovascular health can be

achieved by reducing one’s intake of animal protein, a protein source high in saturated fats. As

society becomes more conscious of better health

habits, there likely will be a shift toward plant protein sources, and a supplementary resource will be

necessary.

Enzymes

The more we learn of the functions and behaviors

of enzymes, the more enzyme technology is being

applied to industrial processes. Marine enzymes,

while almost completely unknown, could be used

beneficially. The industrial process of halogenation

to produce brominated and chlorinated chemicals

is costly, due to the energy needed to activate

bromide and chloride salts to their reactive levels.

Enzymes perform this process in marine algae naturally; thus in principal, marine haloperoxidase enzymes could be used industrially. Hager and

associates (19) have successfully purified

marine halogenating enzyme and illustrated

behavior with numerous substrates.

Industrial Chemical Feedstocks

his

the

its

As oil reserves dwindle, the concept of seeking

industrial chemicals from renewable plant sources

no doubt will be considered seriously. We will need

to turn to plant species that are readily cultured,

have high photosynthetic rates, and contain hydrocarbon resources that somewhat resemble those

found in crude oil. While an “oil-analog” will not

be found, numerous examples of marine algae (both

macroscopic and microscopic) produce mainly linear hydrocarbons. Species are available that could

be cultured to yield hydrocarbon mixtures which

could be used as diesel fuel without further purification. Linear alkanes and alkenes are virtually ubiquitous in marine algae, and these compounds

could be converted (via catalytic cracking processes) to smaller molecules which form the basis

of the modern plastic industry. Marine algae also

have been reported to contain more unusual substances, such as low-molecular-weight sulfides and

amines, as well as industrial precursor molecules,

such as acrylic acid used in the production of plastics and in dentistry (1).

Notwithstanding the work on agar, carrageenan,

and alginate, phytoplankton, in general, have been

virtually unexplored for their polysaccharide comMarine Plants: A Unique and Unexplored Resource • 151 —— ——— .. ———-———-. —.——— —

ponents. A great need exists in this field to develop

products with specific properties not found in existing saccharides. It is highly conceivable that the

thousands of species of unicellular algae would

yield new and important products.

Collection v. Aquaculture?

Marine plant development, whether dealing with

the derivation of pharmaceuticals or industrial or

food-quality chemicals, must be planned in relation

to the most effective source of raw algal materials.

Massive collections of natural seaweed populations

conceivably could be made. While possible, this

generally is unreasonable because limited numbers

of species are found in abundance. Small volume

products, such as a specialty pharmaceutical, could

be developed from naturally occurring populations,

but, in general, effective use of marine algal resources must be coupled with mass culture technology, unicellular algae, in pure form, could not

be collected so must be cultured under controlled

physical conditions. Hence, marine algal resources

development must be closely aligned with modern

advances in algal mass culture.

Mass algal culture and product derivation should

also be developed keeping in mind multiple product

development. The algal resources that should be

considered for development are those that produce

more than one marketable product. Such is the case

with Dunaliella; it yields beta-carotene and glycerol.

This can be extended further to include the possible isolation of lipids (hydrocarbons, triglycerides,

amines, etc.), the simultaneous extraction of watersoluble polysaccharides (products analogous to

agar, etc.,) and, finally, the hydrolysis or digestion

of the remaining material to produce either protein

supplements or crude biomass for energy conversion. Multiple product use will be imperative from

the economic viewpoint to offset the relatively high

production costs.

Problems and Approaches Toward

Developing Marine Algal Resources

A basic problem in considering development of

marine algal resources is that there has been insufficient research on potential products from algae.

Although a significant number of chemical investigations have been conducted on seaweeds, there

have been few on unicellular algae. Many drug candidate molecules are known, but to date few have

been screened as carefully as either pharmaceuticals or agrichemicals.
152 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

The cart has come before the horse to a certain

degree in this field. Considerable resources are being devoted to developing algal culture technologies

in marcroalgae and the unicellular species. However, in most cases these studies are not predicated

on a solid knowledge of subsequent product development, but rather on broader concepts, such as

algal biomass and energy conversion. The time has

come to inititate tedious and costly long-term investigations of the chemical composition of marine

algae, particularly the almost chemically unknown

unicellular forms. Once a framework of sound composition information becomes available, decisions

on what to culture can be made confidently.

A significant problem lies in the poorly developed

working relationships between government, universities, and appropriate industries. Government

funding agencies have difficulty supporting applied

research, particularly as it may benefit a single

private enterprise. The university system finds its

interface with industry strained by patent and proprietary information problems, Therefore, the proper line of basic to applied research, culminating in

real product development, has yet to be achieved.

Renewable resource development with any plant

resource will require close collaboration of the

agencies mentioned above. This is particularly true

in developing marine products because scientists

who have basic research interests will need to be

involved. Federal funding agencies, such as the Sea

Grant Program (Department of Commerce), should

be applauded for providing a structural prototype

which fosters the university-government-industry

interaction.

Biotechnological advance, particularly in the field

of marine genetics, can be expected to have a sizable impact on our use of marine resources, Marine

products and biochemical processes are unique,

and this unique gene pool will be highly useful in

future product development. The algal gene for

agar synthesis, for example, in principle could be

transplanted into a readily culturable nonmarine

organism. These concepts, while futuristic, illustrate the value of the marine algae to yield a wide

variety of unique products.

Conclusions

Marine algae represent a massive resource for

product development based upon their unique genetic adaptations. To foster this development,

however, a greater emphasis must be placed on

basic research into chemical composition, genetics, nutrition, and reproduction, Further, mass

culture technologies must be refined. Collaboration

among governmental agencies that provide funding

must be developed in a tripartite fashion with

universities excelling in marine research and with

new industries. As these components gel into a

more directed exploration of marine algal resources, it seems likely that marine algal species

will become major sources of future products,

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24-503 0 - 83 - 11
THE ROLE OF THE ALKALOIDS OF CATHARANTHUS ROSEUS

(L.) G.DON (VINCA ROSEA) AND THEIR DERIVATIVES

IN CANCER CHEMOTHERAPY

Gordon H. Svoboda*

Indianapolis, Ind.

The search for useful foodstuffs, dyes, medicinal

agents, and other materials from plants, animals,

or minerals is as old as civilization itself. It should

not be surprising, therefore, to learn that all pharmacological prototypes originate from one of these

three kingdoms.

The alkaloids, nitrogen-containing plant bases,

notwithstanding the advent of antibiotics and many

valuable synthetic drugs, constitute an indispensable part of our medicinal arsenal. The manufacture

of alkaloids comprises an important segment of

the fine chemicals industry. Their production is

steeped in tradition, and processes are usually so

highly specialized that it frequently takes years to

establish them on an economic basis.

The author has based his pharmacognosy research on plants having reported folkloric usage

and/or recorded chemical content. After conducting appropriate literature surveys, 440 plants were

chosen for study. One of the plants collected and

investigated was the Madagascar periwinkle, then

botanically known by three names–Vinca rosea,

Catharanthus roseus, and Lochnera rosea. This

plant was reported to produce several desirable

biological effects. Folkloric usage cited the plant as

possessing properties that lowered blood sugar,

thereby making it a possible source of an oral insulin substitute. It also was reported to contain

alkaloids. Related Vinca species were reported to

contain alkaloids and to possess both neurosedative

properties and properties that lowered blood

pressure.

Once obtained, extracts from Catharanthus

roseus elicited none of the reported biological activities. (Eventually, pure compounds were isolated

which did possess the reported properties.) Submission to a cancer screening program showed a profound and reproducible activity against an experimental leukemia model designed to predict clinical

activity against human leukemia. One particular

alkaloid, leurocristine (vincristine), was isolated. It

was effective in treating not only acute lymphocytic

leukemia of childhood but a wide variety of human

neoplasms as well. It has become the “common de-

“Previously with Eli Lilly & Co.

nominator” in most combination therapies, serving as the synchronizing agent.

Classical methods of isolation and purification

were of no value in obtaining the active antitumor

agents from C. roseus; new techniques had to be

devised. Use of selective/differential extraction,

coupled with column chromatography and the gradient pH technique, has resulted in the reported isolation of 74 alkaloids from mature plants and an additional 21 chemical compounds from immature

plants. This research and the results thereof constitute a classic in the annals of pharmacognosy/

photochemistry. Collecting hundreds of thousands

of kilograms of this plant material from the wild

did not seem promising or reliable. As a result, the

plant was cultivated on farms in India and Madagascar. Because a number of variables could seriously threaten the supply of this life-saving drug,

the decision was made to attempt cultivation in the

United States. This was achieved in Texas using

modern growing and harvesting techniques.

To date, attempts for a total synthesis of the active antitumor alkaloids have not been successful.

Synthetic modifications have produced active

agents, none of which have yet replaced the parent

compounds. The drug from C. roseus is one of

many drugs obtained from renewable resources.

The important drug isolated from the Madagascar periwinkle is known scientifically as leurocristine, generically as vincristine, and is marketed by

Eli Lilly & Co., the pharmaceutical house to which

I assigned the patent, as ONCOVIN.

It had been an in-house concept that no anticancer agent would or could ever produce a profit

for the marketing company. The reason was that

cancer is a progressively fatal and emotional disease. (Diabetes can be placed in this category, yet

the financial track record for insulin is substantial.)

Pricing for the marketing of ONCOVIN was designed to recover research and development costs,

not an unreasonable concept.

A company official was reported by William L.

Laurence in The New York Times as saying that

“it will market the periwinkle chemicals at a price

calculated to yield no profit to the company. ”

Nevertheless, ONCOVIN became the highest percent profit item in the Lilly product line, carrying

the relatively insignificant cost-of-sales of 12 per154
The Role of the Alkaloids of Catharanthus Roseus G. Don and Their Derivatives in Cancer Chemotherapy ● 155

cent. ONCOVIN provided an annual profit of several tens of millions of dollars.

It has been estimated that the world contains

500,000 to 750,000 higher order plants, less than

10 percent of which have been even cursorily investigated. The research success potential seems

enormous. However, judicious plant selection must

be coupled with appropriate biological test systems.

In view of the not-for-profit pronouncements of the

company known to have a successful phytochemical screening program, is it any wonder that other

domestic firms hestitate to venture into this seemingly risky endeavor?

Private enterprise in the United States usually has

been factorily innovative. When this occurs, intervention by government or others is unwarranted.

However, government should expose and correct

monumental profiteering. Also, when industry

refuses to do the job, the government should present a choice: either do it with our cooperation, or

we will do it without you. We now stand at this

juncture.

Natural plant products have served as the basis

of man’s medicinal arsenal since time immemorial.

The history of herbal medicine in the treatment of

disease coincides with the history of medicine, and

indeed with the history of civilization itself. Literature citations are recorded for more than 3,000

plant species that have been used or recommended

in various parts of the world for the treatment of

cancer (15).

It has been only within the last 20 years that any

product from a higher order plant has been successfully used in cancer chemotherapy. Oddly enough,

the plant yielding these agents was not included in

the above-mentioned list of 3,000 plants. The isolation of two complex alkaloids—vincaleukoblastine

(VLB) and leurocristine (LC) from the pantropical

plant Catharanthus roseus (L,) G. Don (Vinca rosea

L,) (Apocynaceae)—initiated a resurgence of interest in this area. The success of leurocristine,

termed a “miracle drug” (38), in treating acute

childhood lymphocytic leukemia and a wide variety

of other human neoplasms is well documented.

The following discussion will be restricted primarily to Catharanthus roseus compounds possessing demonstrated utility in the treatment of human

neoplasms, and in a few instances to compounds

considered to have some potential utility on the

basis of antitumor effects in experimental animals.

The true botanical name for the Madagascar periwinkle is Catharanthus roseus (L.) G. Don (33). It has

also been referred to as Lochnera rosea Reichb, and

Vinca rosea L. While the former name has no nomenclatural validity, the latter does, A text has been

devoted to a study of this genus (39). It is important to recognize that Catharanthus alkaloids are

different from Vinca alkaloids and ensure that information is recorded under the appropriate name.

The Madagascar periwinkle, C. roseus, originally

a species endemic to Madagascar (Malagasy Republic), is an erect, everblooming herb or subshrub with

either pink or white flowers that now has a tropical

distribution. It is cultivated as an ornamental plant

in gardens throughout the world.

Independent interest in this plant was generated

by reports of hypoglycemic properties of certain extracts (14). The observation by Noble, Beer, and

Cutts (29) of a toxic depletion of white cells and

bone marrow depression produced in rats by certain fractions of these extracts eventually led to the

isolation of vincaleukoblastine (VLB) sulfate. * Svoboda and Johnson, while screening selected botanicals for experimental antitumor activity, observed

in certain extracts and fractions a reproducible oncolytic activity primarily against P1534 leukemia,

a transplanted acute lymphocytic leukemia, in

DBA/2 mice. This finding eventually led to the isolation of leurosine (35),** a new dimeric alkaloid

closely related in chemical structure to VLB. Subsequently, VLB itself was isolated from the extracts

(21).

Extraction of the

Catharanthus Alkaloids

As with any single plant constituent, the extraction of an alkaloid is an individual problem. While

several standard techniques existed for preliminary

extraction of crude plant materials and subsequent

separation and purification of individual alkaloids,

none of these were applicable to the specific alkaloids of C. roseus. Consequently, a new technique

of “selective” or “differential” extraction had to be

devised (app. I) (36).

This technique differed from the classical approach in that a measure of purification was effected during extraction by forming salts of the

stronger bases in the crude drug on addition of an

aqueous solution of a naturally occurring weak organic acid. Final purification of most of the alkaloids was accomplished by column chromatography on Alcoa F-20 alumina which was partly deactivated with 10 percent acetic acid. This method-

*The United States Adopted Names Committee (USAN) has approved

vinblastine as the generic name for this alkaloid. It is available as

VELBAN, VELBE (vinblastine sulfate, Lilly).

* ● The USAN-approved generic name for this alkaloid is vinleurosine.
l56 Ž Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

ology was responsible for the isolation of leurosine

and VLB sulfate in a single purification step.

The major thrust of the Lilly investigation, however, centered around the early observation that

certain fractions produced an unusually high percentage of laboratory cures. Neither leurosine nor

VLB, nor any therapeutic combination thereof, was

responsible for these cures. Eventually a gradient

pH technique was devised which yielded leurocristine* and leurosidine, * * the two alkaloids responsible for the observed cures (35).

Use of selective or differential extraction, coupled

with column chromatography and the gradient pH

technique, has resulted in the reported isolation of

55 new alkaloids in our laboratories and three

others which were codiscovered by other investigators. To date, 74 alkaloids, three of which we

have never encountered, have been reported as having been isolated from mature plants of C. roseus.

In addition, studies related to alkaloid biosynthesis

involving immature plants have yielded known

monomeric alkaloids, derivatives thereof, and glycosides. A total of 95 distinct alkaloidal entities

have been isolated from this plant (app. II-VII).

One of the basic prerequisites for the successful

isolation of the oncolytic alkaloids from C. roseus

was the availability of a biological monitoring system—i.e., the P1534 leukemia. The use of this experimental mouse tumor as an in vivo assay was

unique to the Lilly Research Laboratories and has

demonstrated how important it is to use strain-specific tumors in inbred animals and to select tumors

that are naturally resistant to most clinically useful

agents. This screening procedure can be of great

value in detecting new agents with different chemical structures. Just as a compound has a spectrum

of tumor specificity, so a tumor maybe said to have

a “spectrum of compound specificity. ”

Structures and Pharmacologic

Activities of Catharanthus Alkaloids

The determination and proof of the various indole and dihydroindole alkaloids structures proved

to be an organic chemist’s dream—virgin territory

involving new entities and heretofore unknown

combinations of ring systems, particularly those

containing the dimeric indole-indoline structure.

It would be remiss not to cite the imaginative and

elegant efforts of German and Neuss in establishing

*The USAN-approved generic name for this alkaloid is vincristine. It

is available as ONCOVIN (vincristine sulfate, Lilly).

● ● The usAN.apprOV~ generic name for this alkaloid is Vinrosidine.

the structures of VLB (app. VIII) and leurocristine

(app. IX) (26). The eventual elucidation of the sterochemistry of these structures [24) has made it

possible to follow a rational approach in studying

structure-activity relationships in this series.

Leurosidine (app. X), the most experimentally active antitumor alkaloid of this group, is isomeric

with VLB (27). The difference is in the indole (“upper”) portion of the molecule; the hydroxy (OH) is

attached to an adjacent carbon (4 I). The epoxide

structure proposed for leurosine (app. XI) by Abraham and Farnsworth (1) has been accepted quite

widely.

Yields of leurocristine are on the order of 0.0003

percent, the lowest yield of any medicinally useful

alkaloid ever produced on a commercial basis. Because yields of VLB are considerably higher, it

would be worthwhile to design an oxidative process to convert VLB into leurocristine. Although

several laboratories have “proven” that this could

not be done, the conversion was in fact accomplished by a method using chromic acid oxidation

at –60° C (22).

While derivatives of alkaloids from higher order

plants seldom, if ever, possess more therapeutic activity than the parent compound, any decrease in

toxicity or side effects can be a valuable contribution. One compound, desacetyl VLB, 4-(N-N-dimethyl-aminoacetate), displayed excellent experimental antitumor activity and possessed far more

benign side effects than those of VLB. Consequently, this compound was selected for clinical testing

(5). While initial results seemed promising, two patients receiving prolonged therapy subsequently

suffered from corneal and lens changes in the eye.

Although a causal relationship was not definitely

documented, clinical trial with this derivative was

terminated (18).

N-Formyl leurosine (app. XII) has shown activity against a series of animal tumors. Some reversible white-cell suppression was observed in rats, but

no signs of neurotoxicity were found in the limited

data reported (32). The latest derivative to stimulate

scientific interest in this area is desacetyl VLB

amide (Vindesine)* (app. XIII), a compound selected from a group of VLB derivatives prepared

by Gerzon and coworkers (8).

Vindesine was selected because, in testing against

tumor systems both sensitive and resistant to VLB

and leurocristine, its spectrum of activity more

closely resembled that of leurocristine than that of

VLB (37). Its acute LD50 dose in mice, 6.3 mg/kg,

*The USAN-approved generic name for this compound is vindesine.
The Role of the Alkaloids of Catharanthus Roseus G. Don and Their Derivatives in Cancer Chemotherapy ● 157

is between those of VLB and leurocristine. No

evidence of neurotoxicity has been observed in

chronic studies in mice, rats, dogs, cats, and

chickens (40).

It is a matter of record that minor molecular modifications in the basic dimeric moiety can produce

dramatic differences in dose-limiting toxicity. Preliminary clinical studies validate this premise;

vindesine’s dose-limiting toxicity involves both

bone marrow and neurological toxicity, thereby

placing it between VLB and leurocristine.

The dimeric Catharanthus alkaloids represent a

new class of oncolytic agents. Attempts have been

made to study their effects on various biochemical

reaction sequences to determine their mode of action. However, the mechanism of the action of these

compounds is still not clearly defined or understood.

These alkaloids appear to affect cell division in

various phases and to varying degrees. This phenomenon has been observed in both in vitro and

in vivo studies (30). Such inhibition can be observed

in the absence of therapeutic response. VLB and

leurocristine seem to elicit similar responses, as do

leurosine and leurosidine.

Studies at the cellular level indicate that many

pharmacologic effects of the C. roseus alkaloids can

be attributed to their completing with tubulin, the

protein component of microtubules and the mitotic

spindle. Substantial evidence indicates that microtubules are important for the substructure and

probably the function of cell membranes. Of the

agents studied, only these alkaloids produce microtubule crystals (7).

Data from various laboratories concerning the

mechanism of action of the Catharanthus alkaloids

appear to conflict in both the techniques and systems used (20,31). A definitive, concentrated effort

at the molecular level, using drug-sensitive tumor

systems, is clearly warranted.

The minor variation in the molecular structures

of VLB and leurocristine has resulted in quite different spectra of tumor specificity in humans for

these two alkaloids. In the relatively short time

since their introduction into the clinic, the dimeric

alkaloids from Catharanthus roseus have become

some of the most valuable agents in cancer chemotherapy. They have proven to be useful as single

agents in the palliative treatment of a number of

advanced neoplasms, and more recently have

played an important role in combination chemotherapy by heightening the action of other antitumor drugs.

The major use of VLB is in treating lymphoma,

particularly in patients with Hodgkin’s disease who

are no longer candidates for high dose, extended

field radiotherapy with curative intent. In single

agent therapy, VLB rivals nitrogen mustard responses in 70 to 80 percent of patients.

VLB is highly effective in the treatment of testicular neoplasms. Objective responses also have been

obtained, albeit with variable frequency, in patients

with choriocarcinoma, neuroblastoma, LettererSiwe disease (histiocytosis X), and metastatic breast

cancer,

The dose-limiting side effect of VLB is bone marrow depression. Temporary loss of hair and constipation are common.

As for vincristine, Taylor (38) says: “Judged by

the usual yardstick of time for the development of

new drugs and their clinical acceptance by physicians, vincristine qualifies as a miracle drug, for

it was only 10 years ago that work was begun on

this compound. Except for the increased activity

in the field of cancer research, the work on vincristine was not abetted like the work on the miracle drug penicillin by a World War. In spite of this,

vincristine is held in high regard by cancer chemotherapists, and much is known of its toxicology,

pharmacology, and clinical activity in the human

being. The worldwide search for plants containing

substances that may inhibit cancer owes much to

the incredibly successful story of vincristine. ”

The most striking feature of leurocristine is its

ability to induce complete bone marrow remission

of 50 percent of children with acute lymphocytic

leukemia. In combination with steroidal hormones,

a 90-percent complete-response rate can be expected. It is also considered to be highly effective

in the treatment of Hodgkin’s disease, Wilm’s tumor, and rhabdomyosarcoma, and is said to be

somewhat effective in the treatment of choriocarcinoma, breast cancer, and primary brain tumors.

Responses against carcinomas of the cervix, prostate, and kidney have also been reported (19).

Despite their extremely great structural similarities,

there appears to be no cross-resistance between

VLB and leurocristine.

Because of its lack of white-cell suppression, leurocristine becomes an excellent candidate in combination cancer chemotherapy. Two to five drug

combinations give higher response rates and more

prolonged remissions than obtained from singleagent therapy. Furthermore, new clinical concepts

involve synchronization of cells in metaphase and

alteration of membrane transport by leurocristine

as an approach to combination therapy.

The dose-limiting side effects of leurocristine are

its neuromuscular manifestations. Prophylaxis of

constipation is indicated. Temporary loss of hair
158 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

is more frequent than with VLB and is dependent

on dosage and duration of treatment.

Children tolerate leurocristine therapy better than

adults. Some treatment centers limit the adult dose

to a maximum of 2 mg per injection. Toxicity is usually reversible, although its manifestations may persist for several months.

The clinical experience with leurosine, both as

the sulfate (2,13,23) and the methiodide (16), has

been more limited than with VLB and leurocristine.

The methiodide was used in clinical trials before

the sulfate because it had greater experimental activity against P1534 leukemia. However, little therapeutic activity was noted, while severe side effects

outweighed the transient tumor shrinkage observed

in two patients (4).

In the case of leurosine sulfate, clinical activity

was evident but at a much lower level than that

of VLB or leurocristine. Leukopenia was less pronounced than with VLB, but was the dose-limiting

toxicity.

Noble and coworkers (28) observed in tissue culture studies that leurosine lysed malignant cells better than VLB and leurocristine when the alkaloids

were added to the culture as sulfate salts in saline

solution. However, the lytic activity of leurosine

was inhibited completely in the presence of adult

human plasma, but not fetal plasma. It was noted

that the inhibitory factor of plasma resided in the

globulins of the adult human plasma. Obviation of

this protein inactivitation in human patients has not

been accomplished and represents a real clinical

challenge.

If the clinical predictivity of the P1534 in vivo

system can be considered valid, leurosidine would

be the most effective Catharanthus alkaloid in

humans. However, its yield from the plant is lower

than that of leurocristine. In addition, doseresponse studies with P1534 leukemia in DBA/2

mice indicate that the optimum dose for complete

cures in 100 percent of the mice is 30 times that

of leurocristine, or 7.5 mg/kg compared to 0.25

mg/kg. Sufficient quantities of leurosidine have

never been stockpiled to allow for a comprehensive

clinical trial. Clinical evaluation had been initiated

several years ago (3), but because supplies were limited was halted before conclusive efficacy was observed. Transient responses and the appearance of

some apparent neuropathy were noted in patients

receiving high doses of the drug. It cannot be considered as having been adequately evaluated by current standards. Sufficient quantities would have to

be provided by an alkaloid modification program,

which has yet to be accomplished.

N-Formyl-N-desmethyl leurosine would not have

been chosen as a clinical candidate on the basis of

experimental antitumor activity in screening programs used in the United States today. However,

it has been reported as producing complete remissions in acute leukemia and partial remissions in

malignant lymphomas, chronic lymphocytic leukemia, and multiple myeloma (10,11). These preliminary clinical studies reveal no neurotoxicity and indicate well-tolerated effects on hemopoietic tissues,

except for transient effects on mature cells of the

granulocytic series. Personal communications regarding its clinical efficacy indicate that cardiovascular complications will preclude its utility as a

single agent entity.

Desacetyl VLB amide (Vindesine) has been in

Phase I clinical trial. In one study involving 3 2

adults with far-advanced neoplasia, it produced

partial remissions in two of nine patients with acute

leukemia, one of four with squamous carcinoma,

and one of four with renal cell carcinoma. No responses were seen in patients with malignant melanoma, colorectal carcinoma, or several other types

of advanced solid tumors. Sixty percent of the patients in this study previously had received Catharanthus alkaloid therapy (6). In a second study,

minor responses were seen in acute lymphocytic

leukemia, acute myelogenous leukemia, hypernephroma, lymphoma, and Ewing’s sarcoma. No

signs of neurotoxicity were observed in children (9).

A recent Phase II single agent study achieved two

complete remissions and four partial responses in

21 patients with advanced breast carcinoma (overall response rate of 29 percent). Results in a pilot

study involving patients with advanced multiple

myeloma resistant to alkylating agents appeared to

be promising. Phase II studies in non-small lung

cancer showed frequent major objective responses

(17).

In the adult patient, vindesine has myelosuppressive activity resembling that of VLB. While the

neurotoxicity produced by vindesine is similar to

that of leurocristine, it is less severe and does not

progress even with continued therapy. Pharmacological studies indicate that vindesine has a larger

volume of distribution, longer serum half-life, and

lower rate of renal clearance than VLB, all of which

may account for the longer duration of marrow suppression induced by this drug (25).

Cancer chemotherapy has evolved over the past

20 years so that it now ranks with surgery and

radiation as a palliative, and in many instances

curative, mode of treating malignant disease. Much

of the improving efficacy of chemotherapy is the
The Role of the Alkaloids of Catharanthus Roseus G. Don and Their Derivatives in Cancer Chemotherapy • 159

result of development of multiple drug regimens.

Initially these drug combinations were derived empirically by selecting agents that had different

mechanisms of action and showed as little additive

toxicity as possible. This empirical approach has

progressed in sophistication to the point where it

is now even possible to use multidrug regimens that

block different discrete segments of the cell cycle.

The Catharanthus roseus alkaloids play an especially important role in these multidrug regimens. Now

that chemotherapy is being developed to augment

surgery on both a pre- and post-operative basis, the

prognosis for many types of human malignancy appears increasingly bright.

Problems and Potentials

Many problems were encountered during the

course of this research, and corresponding solutions were devised. A number have been described;

others follow.

Supplying the hundreds of thousands of kilograms of raw material required per year could have

become a monumental problem, Adequate supply

of the natural plant material had to be maintained.

Original work was performed on the whole plant.

Determination that the desired alkaloids were

found in the leaves allowed for stripping of the

plant, thereby affording a healthier and more profuse regrowth. Collection from the wild eventually progressed to farm or plantation cultivation,

allowing for greater control over growth.

In anticipation that politics would threaten what

had been a reliable crude drug supply, experimental plantings were begun in the United States. New

crop introduction is always risky. The economics

involved are always of major concern. Hand collection and “native” wages are out of the question.

Despite the risk, plantations were started in Texas;

India and Madagascar had lost a viable cash crop.

A forage harvester replaced hand labor and, a

single planting was able to provide several harvests

per season, surviving harvester-cutting with relatively rapid regrowth.

periwinkle cultivation represents a renewable resource, The chemical complexities of the antitumor

alkaloids have to date defied practical total synthesis. When realized, it certainly will require the

ready availability of petroleum-derived starting materials,

The American pharmaceutical industry was built

on and sustained by natural products from the

higher order (chlorophyll-containing) plants. It is

an enigma that little work in this realm is being pursued by U.S. industry, particularly since approximately 25 percent of new and refilled prescriptions

from community pharmacies contain plant products (12).

There is no dearth of plants to be collected and

screened for specific or general biological activity. Of the Earth’s 500,000 to 750,000 higher order

plants, less than 10 percent have been investigated

phytochemically. The investigator has an almost

unlimited choice for selection.

Success potential should be extremely high. However, one must select plants judiciously and must

have appropriate biological test systems available

for monitoring isolation and purification progress.

Plant selection can be based on reported folkloric

usage, but said usage must be rational in both an

investigative and practical sense.

The use of Catharanthus roseus as an oral insulin

substitute previously has been cited. Reports of

usage against hemorrhage, scurvy, as a mouthwash

for toothache, and for healing and cleaning chronic

wounds (36) did not stimulate either scientific or

pratical adrenalin. And yet, these uses could well

prove valuable.

Selection of plants to be tested based on reported

chemical constituents may also be useful. The

author selected alkaloids for research, not only

because of familiarity therewith but also recognition that most medicinal agents of plant origin fall

into this category.

A third, and very valid, category for selection is

a plant which never before has been investigated.

This obviously represents the bulk of selective material. Here again, prudence must be exercised.

Botanical and chemotaxonomic relationships must

be considered.

The fact that major U.S. pharmaceutical houses

are no longer engaged in pharmacognostical/

phytochemical research, particularly as it relates

to palliative/curative measures against human cancer, may well stem from the erroneous concept that

any product would be a “not-for-profit” item. It may

also stem from ignorance on the part of research

administrators who conceive, and most certainly

maintain, that antibiotics will treat or cure all ills,

mainly those designated as “profits.”

The marketplace has been extremely kind to the

periwinkle alkaloids, particularly leurocristine (vincristine, ONCOVIN). It has become the highest percent profit item in the product line of Eli Lilly &

Co., bearing the almost insignificant cost-of-sales

of 12 percent. Yearly sales running into tens of millions of dollars indicate the absolute success of this

natural product, Perhaps public pronouncements
160 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

—

that the item was to be sold “at a price calculated

to yield no profit to the company” misled other

companies that were considering entering the field.

The greatest story never told could well be the

search for an ethereal entity often referred to as “super leurocristine.” This tentative title was bestowed

upon it by virtue of experimental antileukemic activity. Typical leurocristine/leurosidine fractions

exhibited activity on the order of three survivors

at a dosage of 0.3 mg/kg. “Super” fraction activity

was of the order of three survivors at 0.0009 mg/kg,

representing a 300-percent increase in activity (or

decrease in dosage).

Workup of “super” material failed to yield any

new crystalline compounds. The press of readying

leurocristine for clinical trial and subsequent

marketing prevailed over investigative matters. Besides, equivalent material was being stockpiled for

later investigation, thereby affording larger quantities for workup, Unbelievable as it seems now,

and most certainly at the time, these stockpiled

materials were discarded in an unsanctioned and

misguided cleanup effort.

Because of processing changes which were constantly being initiated, no such “super” material

could again be stockpiled. Efforts to repeat the original process for stockpiling purposes were denied,

as certain cost projections for “experimental processing” were prohibitive. If the problem of human

cancer were solved, the search for “super leurocristine” would probably be a matter of scientific semantics, but the problem has not been solved, and

the challenge must be met.

1. Abraham, D. J., and Farnsworth, N. R., “Structure

Elucidation and Chemistry of Catharanthus Alkaloids. III: Structure of Leurosine, An Active Anticancer Alkaloid,” J. Pharm. Sci. 58:694-698, 1969.

2. Amiel, N,, Bernard, J,, Besis, M., Dreyfus, B., Najean,

Y., Seligmann, M., and Pequignot, H., “Acquisitions

recentes clans la chimiotherapie des cancers, ” Presse

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3. Armstrong, J. G., and Dyke, R. W., Lilly Clinic, Indianapolis, Ind., personal communications.

4. Armstrong, J. G., Dyke, R. W., and Fouts, P. J., Lilly

5

6

Clinic, Indianapolis, Ind., unpublished observations.

Armstrong, J. G., Dyke, R. W., Fouts, P. J., Hawthorne,

J. J., Jansen, C. J., and Peabody, A. M., “Initial Clinical

Experience With Vinglycinate Sulfate, A Molecular

Modification of Vinblastine,” Cancer I?es. 27:221-227,

1967.

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I. Taylor and Norman R. Farnsworth (eds.) (New

York: Marcel Dekker, Inc., 1975), pp. 209-236,

Cullinan, G. J., Gerzon, K., Poore, G. A., and Sweeney,

M. J,, “Inhibition of Experimental Tumor Systems by

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386-425, 1967, 1968, 1969, 1970, 1971.

Hodes, M, E,, Rohn, R, J., Bond, W. H., and Yardley,

J., “Clinical Trials with Leurosine Methiodide, and

Alkaloid From Vinca rosea Linn., ” Cance r

Chemother. Rep. 28:53-55, 1963.

Internationals Vinca-Alkaloid-Symposium, Eldisine

fVindesin), Frankfurt/Main, November 1980.

18. Jansen, C. J., Jr., Eli Lilly & Co., Indianapolis, Ind,,

personal communication.

19. Johnson, I. S., “Plant Alkaloids, ” Cancer Medicine,

Volume 11, James F. Holland and Emil Frei III (eds.)

(Washington Square, Philadelphia: Lea and Febiger),

in press.

20, Johnson, I. S., Armstrong, J. G., German, M., and Burnett, J. P., Jr., “The Vinca Alkaloids: A New Class of

Oncolytic Agents,” Cancer Res. 23:1390-1427, 1963.

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Jovanovics, K., Szdsz, K., Fekete, G., Bittner, E,,

Dezberi, E., and Eles, J., “Chromic Acid Oxidation

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3,899,493, 1975.
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Hodgkin’s Disease, Acute Lymphoblastic Leukemia,

and Lymphoblastic Lymphosarcoma, ” Cancer Chemother. Rep. 49:47-49, 1965.

Moncrief, J. W., and Lipscomb, W. N,, “Structure of

Leurocristine Methiodide Dihydrate by Anomalous

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Nelson, R. L., Root, M. A., Dyke, R. W., and Ahmadzai, S., “Pharmacokinetics of Desacetyl Vinblastine

Amide (Vindesine) in Man, ” Proc. Amer. Assoc.

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on Nucleic Acid Formation by Isolated Cell Suspensions,” Cancer Res. 26:876-881, 1966.

32. Somfai-Relle, S., Ndmeth, L., Jovanovich, K,, SZASZ,

K., Gtil, F., Bence, J., Tdth, K,, and Kellner, B., “New

Vinca Derivative With Antitumor Activity:

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ton, D. M., “The Preclinical Study of De~acetyl Vinblastine Amide, ” Proc. Amer. Assoc. Cancer Res.

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E., Katner, A. S., Miller, J. C,, and Neuss, N., “13 CNMR. Spectroscopy of Naturally Occurring Substances. XXXII: Vincaleukeblastine and Related Alkaloids,” Helv. Chim. Acta 58:1560-1567, 1975.
162 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

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The Role of the Alkaloids of Catharanthus Roseus G. Don and Their Derivatives in Cancer Chemotherapy . 163
164 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

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The Role of the Alkaloids of Catharanthus Roseus G. Don and Their Derivatives in Cancer Chemotherapy ● 165

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166 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

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The Role of the Alkaloids of Catharanthus Roseus G. Don and Their Derivatives in Cancer Chemotherapy ● 167

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168 ● Plants:: The potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Appendix Vii. —Alkaloids isolated From C. roseus

From Biosynthesis Experiments

Alkaloi d

19-Acetox y

-

1 1

-

hydroxy tabersonin e

19-Acetox y

-

1 1

-methoxy tabersonin e

N-Acetylvincosid e

Ajmalicin e

Akuammicin e

Catharanthin e

Cathenamin e

Coronaridin e

Corynanthein e

Corynantheine Aldehyd e

4,21-Dehydrogeissoschizin e

l9-Epi-ajmalicin e

19-Epi-vindolinin e

Gelssoschizin e

Horhammericine

Horhammerinine

Isovincosid e

11-Methoxytabersonin e

Preakuammicine

Stemmadenine

Strictosidine lacta m

Tabersonin e

Vallesiachotamin e

Vincosid e

Vindolin e

Appendix IX

H

I

C H3 0

I

Appendix

Appendix Viii

OH

CH3 C02CH3

I

C H30

I

C H3 C 02C H3

R C02C H3
The Role of the Alkaloids of Catharanthus Roseus G. Don and Their Derivatives in Cancer Chemotherapy ● 169

H

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Appendix XII

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24 - 503 O - 83 - 12
STRATEGIC AND ESSENTIAL industrial MATERIALS FROM PLANTS

THESIS AND UNCERTAINTIES

Howard C. Tankersley

Soil Conservation Service

U.S. Department of Agriculture

Washington, D.C.

and

E. Richard Wheaton

Science and Education

U.S. Department of Agriculture

Washington, D.C.

Strategic and Essential

Industrial Materials

The United States depends on other nations for

a broad range of materials and manufactured products important to U.S. industry. Among these are

agriculturally produced plant substances and

mined materials, including petroleum. This paper

is concerned with products that are or could be

agriculturally produced in the United States and

used as industrial materials or as renewable replacements for petroleum as sources of feedstock

in the chemicals industry.

Three of these industrial materials are classified

by law as “strategic,” meaning critical to our national defense. These are natural rubber, castor oil,

and sperm whale oil. The Defense Production Act

of 1950 as amended in 1980 (Public Law 81-774) requires that sufficient supplies of these materials be

acquired and stored in the United States to meet

national defense needs in case of war. The costs

of acquisition, storage, and replacement are borne

by the Federal Government, which must manage

the stocks so they do not interfere with the marketplace for these commodities. Stockpiles are used

only for meeting military needs and are not available to meet emergency civilian needs. “Essential”

materials are those required by industry to manufacture products depended upon daily. Essential

materials include the strategic materials, waxes,

resins, oils, gums, newsprint, other items manufactured or extracted from plants, and replacements

for petroleum used as feedstock in manufacturing

synthetic organic chemicals, plastics, industrial

coatings and paints, printing inks, surfactants, and

synthetic fibers,

Thesis and Purpose of the Paper

This paper will present and discuss some of the

policy issues related to use of U.S. land, capital, and

labor to meet the Nation’s long-term needs and to

170

reduce dependence on other nations for strategic

and essential industrial materials. The thesis is that

the United States can move industrial dependence

on a finite resource (petroleum) to renewable ones

(agriculturally produced feedstocks).

Available Data

Comprehensive data on imports of agricultural

commodities are available from the Agricultural

Statistics series published annually by the Department of Agriculture (5). The United States International Trade Commission provides comprehensive information on total imports of petroleum and

on total domestic production of synthetic organic

chemicals. Chemical data on plant extracts are

found in publications of the Department of Agriculture, Agricultural Research Service’s Northern

Regional Research Laboratory (Center) at Peoria,

Ill. The level of confidence in all these sources is

high. Examples are shown in table 1.

Other data used in this paper represent estimates

rather than “hard,” quantifiable figures. For example, the total amount of plant material and various

precursor chemicals imported for use in U.S. industry to produce essential industrial materials is

not recorded and must be estimated. Similarly, although the total amount of petroleum imported is

known, the amount that might be replaced by renewable sources of feedstock in manufacturing

chemical products must be estimated. The best

available estimates now are thought to be those

made by research chemists in the Department of

Agriculture. These are shown in table 2.

Much of the information presented in this paper

is synthesized from papers published in refereed

scientific journals over a period of 10 or more years,

from monographs available from the Agricultural

Research Service, and data collected by a task force

of USDA’s Science and Education Administration

(SEA) personnel established to explore the USDA/

SEA role in strategic and essential industrial

materials research (7).
Strategic and Essential Industrial Materials From Plants—Thesis and Uncertainties • 171

Lists of Imports for Which There May Exist Domestic Production Alternatives

That Could Be Implemented In Ten Years

Table I.—Agricultural imports-1978 Table 2.–Estimates of Nonagricultural imports-1978

—

Produc t

Natural Rubbe r

Vegetable Oils and

Waxes

Cast or $40.0

Palm $74.9

Palm Kernel $34. 8

0liv e $36.8

Coconut $228. 9

Natural Waxe s

Cocoa Butte r

Fibers (Other tha n

cotton or jute )

Value of Imports Value of Imports

($ Millions ) Produc t ($ Millions )

$665.9 Synthetic Rubbe r $148. 9

$458. 0 Plastic s $517 ● 5

Synthetic Fiber s $238. 2

Pharmaceuticals $292. 3

Dyes, Tanning Agents $170. 7

Petro Waxe s $47. 5

Coatings and Printin g $40. 0

Ink s

$9*3 Adhesive s $100. 0

$96. 1 Detergents, Surfactant s $483. 0

$28. 2 TOTAL $2,038. 1

Drugs (Agricultural ) $137. 1 SOURCE: Data sheets prepared by scientists at the USDNARS Northern Regional

Essential Oil s $82.1 Laboratory at Peoria, Ill, for a Science and Education Aministration Task Force on Strategic and Essential Industrial Materials; March

Oilseed and Product s $508. 3

1980, Data sources used varied and included issuances by the US.

International Trade Commission and that collectedly scientists from

TOTAL $1,985. 0

trade publications and firms The study was intended to be illustrative

rather than definitive

In addition, the US imported an estimated $35 billion worth of newsprint

SOURCE: Agricultural Statistics 1980; Department of Agriculture, Government

Printing Office, Washington, DC., 20402.

NOTE Agricultural imports figures for 1979 are 129 times the 1978 figures The estimates of nonagricultural chemicals Imported for 1979 are 1.15 times the 1978 figures

The trend in expenditures for agricultural imports, 1975-79, is mixed —essentials up 43 percent over the 5-year period, cocoa butter up 170 percent, drugs up 72 percent,

and natural rubber up 127 percent, while expenditures for vegetable oils and waxes and for oilseeds remained about even Expenditures for fibers other than cotton

and jute declined during the period

Discussion is limited to potential agricultural

crops for which sufficient research indicates that

their domestic production and use in the chemicals

industry is chemically feasibile, agronomically possible, and economically viable, This paper, therefore, must be considered illustrative rather than

definitive. Significantly more agronomic and economic research must be undertaken before definitive conclusions can be reached. At the same time,

however, urgent public policy issues must be addressed promptly if our Nation is to have an assured supply of strategic and essential materials.

Importance to the United States

The United States imported an estimated $22.1

billion worth of agriculturally produced industrial

materials and petroleum for feedstock during 1978;

the figure for 1979 was slightly over $23 billion. The

trend for the period 1975 through 1979 was an average annual increase of about 10 percent according

to data in Agricultural Statistics 1980 and estimates

made in 1980 by Department of Agriculture researchers in industrial chemistry. The Nation could

spend an additional $1.1 billion or more (1979 dollars) over the next 18 years acquiring and maintaining strategic stockpiles of natural rubber and castor

oil (2).

In 1978, U.S. industry manufactured over 84.6

million metric tons (MT) of synthetic organic chemicals valued at about $754 per MT, for a total of

about $63.8 billion (9). The manufacture of these

chemicals consumed about 470 million barrels of

petroleum, valued at about $15.1 billion, as

feedstock (6). U.S. industry also purchased nearly

$2 billion worth of agricultural imports including

natural rubber, seed and vegetable oils and waxes,

cocoa butter, fibers other than cotton or jute, drugs,
172 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

and essential oils. In addition, the United States imported an estimated $3.5 billion worth of newsprint

and other paper products and $2.05 billion worth

of chemicals extracted from plants (about 50 percent) or made from petroleum (about 50 percent) (7).

Technologically, it is possible to produce domestically nearly all the aforementioned imported agricultural products and materials and to substitute

domestically produced agricultural products for the

470 million barrels of imported petroleum feedstock. It is estimated that increased farming operations to produce these agricultural substitutes

would consume an additional 200 million barrels

of petroleum for fuel and agricultural chemicals;

therefore, the net savings would be about 270 million barrels of imported oil per year.

Production of only one-third the annual domestic

demand for strategic materials (natural rubber, castor oil, and sperm whale oil) would eliminate the

need to stockpile them.

According to the Federal Emergency Management Agency, the national stockpiling requirement

for natural rubber is about 800,000 MT. The stockpile contained about 100,000 MT in 1980, leaving

a shortfall of about 700,000 MT. World production

of natural rubber has been declining slightly and,

on an annual basis, is only keeping pace with world

demand. The annual demand of the United States,

the largest single user of natural rubber, greatly influences the world supply-demand formula each

year. Therefore, each time the United States attempts to purchase rubber for the strategic stockpile, the result is a dramatic increase in price. At

the 1978-to-1982 average price for natural rubber

($1,287 per MT), acquisition of the rubber needed

to meet the 800,000 MT stockpile requirement

would cost the Federal Government about $900 million. Storage and management costs for this stockpile would run an estimated $7 million per year.

Total costs, at constant 1982 dollars between now

and the year 2000, would be slightly over $1 billion.

If the United States domestically produced 270,000

MT of natural rubber per year, the need for stockpiling would not exist.

The stockpiling target for castor oil is about 9,981

MT. The present stockpile contains about 5,671

MT. Acquiring the 4,310 MT shortfall would cost

an estimated $5.2 million. Acquiring and storing

the material through the year 2000 would cost about

$13.8 million (1979 dollars). Domestic production

of one-third the annual U.S. demand (about 10,000

MT) would eliminate the stockpiling need.

Sperm oil is obtained from the sperm whale, an

endangered species. Since U.S. law prohibits production or importation of sperm whale oil, the Nation has no stockpile of sperm whale oil. Alternatives are available and can be provided domestically.

Producing 100 percent of the strategic and essential industrial materials or their replacements

would reduce U.S. foreign outlays by about $16.5

billion annually at constant 1979 dollars and demand levels. Savings for different levels of domestic

production can also be calculated. In addition, domestic production of one-third the U.S. demand for

these three strategic materials would save more

than $1 billion of public money over the next 18

years (money that otherwise would be spent in acquiring and maintaining strategic stockpiles of natural rubber and castor oil) and would provide replacements for sperm whale oil. Such a program

would increase demands for domestic agricultural

production, thus transferring expenditures for foreign petroleum, chemical, and agricultural imports

into expenditures for domestic agricultural products.

The United States has about 413 million acres of

cropland and about 36 million acres of pasture and

other land in farms that easily and inexpensively

can be converted to crop production. This represents an immediately available crop production

base of about 450 million acres (8). In 1979,

America’s farmers used 348 million acres for crop

production: an uneconomically low use rate of

about 77 percent. Production of substitutes for onethird to one-half the industrial materials purchased

abroad would demand about 60 million acres of

cropland, Production of food and fiber at the 1979

rates plus production of these materials would require 408 million acres of cropland: a utilization

rate of nearly 91 percent. A problem would be the

propensity for opportunists to produce commodities on fragile soils in years when prices are high

and to abandon them in years of lower prices, leaving the State, Federal, or local government to pick

up the costs of dealing with stream siltation, severe

blowing of soils, encroachment of undesirable plant

species, and other problems. A mechanism to prevent such practices, but achieve a 91 percent utilization rate of the U.S. cropland base, would have to

be found.

The Nation has about 96 million additional acres

of land that could be converted to crop production

with more difficulty and expense than the 36 million acres cited above. Therefore, the Nation’s total

cropland base, or that land capable of sustained

crop production under intensive cultivation by

known methods, is 540 million acres. According to
Strategic and Essential Industrial Materials From Plants— Thesis and Uncertainties ● 173 —

projections made by the Department of Agriculture

(4), about 462 million acres of cropland will be

needed in the year 2030 to meet domestic and

foreign trade demands for food and fiber. This

would leave 78 million acres of the cropland base

to meet other production needs, assuming that this

base is not converted to urban and other nonagricultural uses, Use of 462 million acres for food and

fiber production and 60 million acres for industrial

materials production would represent a 96.8 percent utilization rate of the Nation’s cropland. At

that rate of use, it might be possible to eliminate

commodity support and subsidization programs for

food and fiber,

It is technologically possible to provide domestic

agricultural substitutes for nearly all the imported

agriculturally produced industrial materials and a

large share of the petroleum used as feedstock in

the chemicals industry. The following table lists

some of the potential domestic crops and what they

might replace.

In addition to those plants identified in table 3,

a number of others might be used to provide replacements for feedstocks in the chemicals industry, For example, research has already established that Limnanthes, Lunaria, Valeriana, Cuphea, and Foeniculum are potential sources of specific acids, esters, and oils used in industry. In addition, oils from existing agricultural crops such as

soybeans, safflower, sunflower, linseed, corn, and

other oilseed and vegetable oil crops could be used

for certain industrial purposes.

Agronomic Potential

Development of the agricultural crops discussed

herein could benefit nearly all of the Nation’s agricultural areas, Guayule and jojoba, perennial aridzone plants, can be produced in the arid Southwest.

Crambe is a short- season annual crop which might

be double-cropped in the major production areas

of the Midwest, South, and Southeast. It would provide an alternative to corn or wheat in areas marginal for these crops. Kenaf, a dense-growing annual, is commercially valuable for making newsprint and other paper and fiber products. Cuphea,

an annual, now is grown experimentally in Germany and the United States. It should adapt well

to Northcentral, Northwest, Northeast, and Pacific

Northwest United States. Stokesia could be produced in the Southeast, and Vernonia in the

southern tier. Lesquerella could be grown in Central, Southcentral, and Southwestern United States,

while Linmanthes is adapted to the Pacific Northwest, Both are annuals, Lunaria seems to be

adapted to northern regions with long days and

eventually might provide a crop for Alaska. Some

Table 3.—Potential Domestic Crops and Uses

— —

Guayul e Hevea natural rubber, resin s

Crambe High erucic rape oil an d

petroleum feedstoc k

Jojob a Sperm whale oil and imported waxe s

Lesquerell a Castor oi l

Vernoni a - Stokesi a Epoxy oil s

Kena f Imported newsprint and pape r

Assorted oilseed s Petrochemicals for coatings an d

other industrial product s

—

SOURCE: L H, Princen, Alternate /ncfustr/a/ Feedstocks From Agr/cu/ture (Peoria, Ill.: Northern Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, 1980).
174 . P/ants: The potentials for Extracting Protein, Medicines, and Other Useful Chemicals—workshop Proceedings

Lunaria lines are biennial and some are annual,

(The above paragraph is taken from Princen (3).)

Current research on the above plants is extremely limited, A little genetics and agronomic work is

being done. Less is being done on use of meals and

other byproducts, including cellulose, left after extraction of the principal products. Guayule, jojoba,

and crambe are being grown on semicommercial

scale acreages. Limited plant breeding and agronomic research is under way for these three potential commodities. Some small-scale seed increase

and agronomic work is under way with Lunaria

and Limnanthes at universities in Oregon and

Alaska. Limited commercialization work on jojoba

is being done by the private sector and universities

in the Southwest. Federal funding for research is

greatest for guayule, a source of natural rubber,

because of its importance to the military. However,

the total 1981 expenditures committed to guayule

research totaled only about $3 million, Research

commitments to all other potential substitute commodities discussed herein were considerably less,

Little additional basic chemical research is needed for the commodities discussed in this paper. The

next level of research would involve chemical engineering to develop efficient, economical extraction and processing systems, an area of proprietary

interest in the private sector. Such research is

needed, but if it is to be undertaken at public cost,

arrangements will have to be made to sell, franchise, or license the processes for exclusive use by

firms. Because of the present lack of risk capital in

the private sector, public support of such research

probably would be necessary if these plant materials are to be commercialized. However, current administration policy appears not to favor public sector support for agricultural research of this nature.

In 1982, the Office of Management and Budget imposed rigid guidelines governing Federal research

and directed the Department of Agriculture to terminate any ongoing research commercial in nature

(l). Significantly, an article in The Washington Post

during the week of November 8-12, 1982, noted that

a White House report justified continued research

on the space shuttle because of its commercial potential. It is interesting to note that the latest flight

of the space shuttle, which the news media reported

cost the government about $250 million, collected

an estimated $38 million from private industry as

fees for putting two satellites into orbit. If that is

considered the commercial value of the flight, one

may conclude that the other $212 million must be

charged off to research and development, a subsidy

to the private sector. Needed subsidies to develop

agricultural materials substitutes would be modest

by comparison.

The most needed research on these potential

commodities in the immediate future is in the areas

of plant breeding and agronomy. Byproduct use research also will be needed. It is not difficult to

calculate the price at which plant oil extracts must

be sold to compete with petroleum feedstocks in

the chemicals industry, but the value of the meal

and other byproducts are unknown because information on their possible uses is limited. This knowledge is vital to assessing commercialization potential. For instance, the late 1982 price of soybean oil

was about 17.2 cents per pound, and the value of

the meal was about 8.8 cents per pound. Total value

of the processed commodity was about 26 cents per

pound, At a price of $6 per bushel, soybeans sell

for about 10 cents per pound off the farm. If there

were no value in the meal, the farm price would

have to be less to make processing the oil profitable.

Such information is needed to assess the economic

feasibility of commercialization, Enough work has

been done on byproducts of commodities discussed

in this paper to suggest that they may have values

similar to those of byproducts from soybeans and

other conventional oil crops.

Most of these new crop materials now being

grown in research projects are from wild or nearly wild plants. Genetic improvements are needed

to increase seed and oil yields and predictability

of the plant under cultivation, In the absence of

such genetic improvements in corn, average U.S.

annual yields from unimproved stocks might be 8

to 10 bushels per acre, rather than the 109 obtained

for 1979 from improved hybrids. While tenfold increases in crambe production are unrealistic, twofold increases are feasible. A threefold increase in

seed yield and a 10-percent increase in oil yield,

calculated from the average of present yields in different States, would produce 5,400 pounds of seeds,

2,700 pounds of oil, and 2,700 pounds of meals and

other products per acre, Research is needed on how

to cultivate the plant to obtain optimum yields of

both seed and oil,

Little agronomic research has been done for potential new commodities other than crambe and

guayule. Yield data from test plots reflect only initial efforts to cultivate plants using strains of seed

that have not been genetically improved.
Strategic and Essential Industrial Materials From Plants—Thesis and Uncertainties ● 175

Economic Potential

Several factors must be integrated to estimate the

economic benefits of using domestic production to

replace agricultural imports and to substitute renewable agricultural materials for petroleum as

feedstock in the chemicals industry.

Paramount is the question of the relative costs of

substitutes and current sources of these materials.

Next in importance is the degree of profitability in

producing new agricultural raw material. The third

major factor is the level of subsidization required

by the agricultural industry to meet national strategic and essential materials needs.

The National Science Foundation and the Midwest Research Institute, in cooperation with universities in the Southwest and rubber companies, completed an exhaustive study of the commercial feasibility of establishing a domestic natural rubber industry based on guayule. According to that study,

the price of imported rubber is expected to rise in

the foreseeable future, particularly if world supplies

continue to dwindle. The study estimates that the

price for imported rubber and the costs of domestic

production will converge in the late 1980’s, making it equally as attractive economically to produce

domestically as to import the material. The advantage of not having to import a strategic commodity over distant sea lanes in times of emergency is,

of course, great.

Sperm whale oil is not legally available in the

United States, and U.S. policy discourages foreign

production; therefore, a substitute for this highquality lubricant must be provided. Jojoba is an

ideal substitute. Jojoba can also be a substitute for

castor oil. Castor oil currently costs about 54.5 cents

per pound. While castor oil has been produced in

the United States, the bean contains toxic and

allergenic properties that pose hazards for people

and animals and problems for waste disposal. Its

domestic production has, therefore, been discontinued. Lesquerella is another substitute for castor

oil. Its cultivation poses no health hazard, and the

meal can be processed for animal feed.

The primary economic consideration in substituting agricultural commodities for petroleum as

feedstock in the chemicals industry is the price of

petroleum. Currently, petroleum is imported at a

price of about 10.6 cents per pound. In industrial

uses, seed oils could sell at a higher price per pound

than petroleum without increasing the price for the

final chemicals produced. These plants yield chemicals in relatively pure form so that they can be used

with little processing. Extraction of the same chemicals from petroleum is complex and expensive.

The only true comparison of costs and feedstock

values can be made when the value of the acids,

esters, waxes, or other chemicals produced from

the two different sources of feedstock are compared. This comparison cannot be made until semicommercial agronomic production is undertaken

and engineering processes for extracting these new

plant oils, at the prototype scale, are developed and

tested. This will allow accounting for the total processing, agronomic production, and other costs to

define total costs at the prototype and commercial

scales of production.

Some cost projections can be made on the basis

of available data. For example, initial attempts at

production of crambe on semicommercial acreages

in western Kentucky yielded 1,800 pounds of seed

and 720 pounds of oil per acre. At the current price

of petroleum (10.6 cents per pound), the oil from

an acre of crambe would be worth $76. If one assumes that this oil is 25 percent more valuable as

feedstock than petroleum because it requires less

costly processing, its value would rise to $95 per

acre. This compares favorably with the economic

returns from wheat production of 30 bushels per

acre in the same area. With even minimal increases

in production, crambe might become an attractive

substitute for current crops that are only marginally

adapted to certain geographical areas. However,

suppose research can triple the seed yield and increase oil content by 10 percent; then the crop

would be valued at $286 per acre based on the current competitive price of imported petroleum. In

addition, the meal can be fed to beef cattle. With

a 25-percent value increase based on lower processing costs than petroleum, the value would rise to

$357 per acre. Taking the average yield and mean

price for corn in the United States during the past

5 years, corn for grain would be worth about $252

per acre. An assessment based on economics alone

then might favor growing crambe over corn in that

area.

During recent years, the Federal Government has

spent between $7 billion and $14 billion annually

to subsidize production of commodities that are

already in surplus. If this subsidy were spent instead to encourage the domestic production of imported plant materials or to provide substitutes for

petroleum feedstocks in the chemicals industry, the

average subsidy on the 60 million acres would fall

between $116 and $233 per acre per year.

Some estimates may also be made regarding the

effects of a successful program to substitute domestic production for importation and agricultural

commodities for petroleum feedstocks. If 60 million

acres are used to produce such commodities, on-
176 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

farm employment would increase by about 155,000

jobs, or about 7 percent over 1979 farm employment. The 60 million acres is equal to 133,333 average-sized farms, each employing 1.618 workers. If

the assumption that one job in agriculturally related

enterprises (transportation, processing, machinery

and equipment, agricultural chemicals, sales, and

management) will be created for each new onfarm

job, the total job increase would be about 311,000.

(In the combined agricultural and food industries,

there were about 17 million workers in 1979, but

only 2.7 million onfarm. This is a ratio of 6.2 to 1.)

At average rates of use, these hypothetical 133,333

“new farms” would need 253,000 tractors; 173,000

trucks; about 120,000 harvesters of various kinds;

and related equipment. Thus the benefits would

spill over into the manufacturing sector. At averageuse rates for all farms, production would consume

about 2.9 million tons of fertilizers and about 200

million barrels of petroleum in addition to other

products and services. (These figures were calculated from data contained in Agricultural Statistics

1980.)

Another consideration must be the impact on

world demand and price for OPEC petroleum if the

United States reduced its demand by nearly 740,000

barrels per day (270 million barrels per year). Evidence suggests that oil conservation efforts in the

United States and other importing countries already have had major dampening effects on world

production and pricing. This factor represents approximately 4 to 5 percent of our annual consumption of petroleum. However, should substitution of

agricultural commodities drive down the price of

oil, there would be incentive to switch back to

petroleum as feedstock. Conversely, if the price of

oil continued to rise, there would be incentives to

switch back to agricultural substitutes.

In the event the world oil price decreased as the

United States switched to agricultural alternatives,

the United States would have increased leverage

with suppliers as long as its option to substitute

agricultural commodities were kept open. At this

point, the issue would become a political rather

than economic one.

Political Considerations

Political considerations underlying this issue

revolve around two central questions: 1) what does

the United States have to gain and lose in the international community, and 2) whose ox will get

gored?

Exporting nations presumably would react unfavorably if the United States chooses to substitute

domestic production for imported agricultural materials and petroleum. On the other hand, nations

competing with the United States for these resources in the world market would be happy. Those

who compete with the United States for marketing

their food and fiber also would be happy. The complex effects of such a substitution strategy on any

one nation are calculable but beyond the scope of

this paper. Given that such effects can be calculated, the decision whether or not to substitute is

as much political as it is economic.

On the domestic front, the key short-run issue for

farmers, agricultural firms, and the Federal Government will be whether to subsidize production of

new agricultural commodities instead of continuing to subsidize surplus production or support

agreements to take land in surplus commodities out

of production. As for defense, the issues are: 1) how

much should we invest in stockpiling materials as

opposed to encouraging domestic production of

strategic materials to avoid stockpiling needs, and

2) what is it worth to have domestic control of strategic materials supplies?

Public policy discussion will be strongly affected

by private sector concerns. Domestic production

of these commodities will not be in the short-run

interest of vertically integrated firms now producing chemicals from petroleum feedstock, or of those

firms now importing and supplying such agricultural materials. However, the negative interest of

these firms in the issue might be offset by the positive interest of industrial users of such intermediate

chemicals and other products. For instance, the

news publishers could be highly interested in shifting from imported newsprint and other paper to

domestically produced paper, since current data

suggest it can be produced domestically for less

than the cost of importing it. It is possible that users

of intermediate chemicals or finished products

(coatings, paints, and printing inks) may encourage

substitution if a superior or less costly product can

be obtained in the long run, if the rate of price fluctuation is decreased, or if assurances of continued

supply are increased. Consumers of the final products might be expected to support substitution if

assurance of supply is increased, the rate of price

fluctuation is decreased, and the general economy

is benefited. This includes anyone who owns a

house, paints an apartment, owns a car or household appliances, uses cosmetics, holds a job, purchases a toothbrush, or wears clothes made totally

or partly of synthetic fibers. Military leaders might
Strategic and Essential Industrial Materials From P/ants—Thesis and Uncertainties . 177

be expected to support domestic supply of strategic

materials,

Policy Shifts Neede d

Four domestic policy shifts are needed to facilitate any move toward domestic control and production of strategic and essential industrial materials.

The first is from dependence on foreign nations for

agriculturally based strategic materials to domestic

supply of them. The $1.1 billion that would otherwise be spent acquiring and maintaining these

stockpiles should be committed to this end.

The second shift is to a national policy of encouraging agricultural research that has foreseeable

commercial application including participation

with the private sector in commercialization activities, partly research and partly commercial in

nature. Federally supported research should be able

to take commercialization through the prototype or

pilot scale of activity under conditions that assure

private sector partners exclusive rights to use patentable processes or products for a period of time,

thus allowing the firm to recapture its investments.

The third domestic policy change needed is to

spend federal funds to support production of useful

agricultural commodities rather than supporting

production of surplus commodities or for paying

farmers to discontinue production.

The fourth domestic policy change needed is to

look at domestic production of agriculturally produced materials as a way of using our farm production potential rather than depending on foreign

trade. The United States, along with most of its

allies and friends, is competing for a limited foreign

market with surplus commodities,

On the international scene, the government may

have to be prepared to limit, initially, the import

of petroleum to encourage U.S. firms to substitute

domestically produced agricultural commodities.

The reduced demand should provide increased leverage in negotiating prices for the remaining

imports,

conclusion

On the basis of “best case” assumptions, the

chemical technology exists to substitute domestically produced renewable agricultural commodities

for about 170 million barrels of petroleum annually and for about $6.3 billion worth of imported agriculturally produced materials. There is a potential

to reduce expenditures by about $1.1 billion over

the next 18 years for stockpiling natural rubber and

castor oil and for providing a substitute for sperm

whale oil. The possibility of finding a more constructive use for the dollars spent in maintaining

our agricultural production capability also exists,

No further research on the basic chemistry of

these materials is needed, What is needed now is

research related to the agronomic of producing

such commodities, plant breeding to improve seed

and oil or fiber yields, and research into byproduct

use. In tandem with these efforts, economic feasibility assessments and/or definition of the economic

parameters for commercialization are needed.

Research or commercialization activities in partnership with private firms should be undertaken

to develop prototype processing or other production facilities, Such commercialization activities

must have an educational component. Industrial

chemists are trained in the chemistry of using

petroleum as feedstock. In the early development

of the chemicals industry, plant materials and coal

were used as feedstock. Farmers who might become involved in producing the plant materials for

use in commercialization research will not know

the best cultural practices.

It would not make sense for the United States to

jump headlong into a substitution program, but sufficient resources should be committed to the kinds

of activities suggested above to use or discard, with

just cause, the many development options that exist.

1. Colorado State University, Diversity (a news journal

for the plant genetic resources community), vol. 1, No.

2, June-July 1982, p. 1.

2. Hall, L., the Federal Emergency Management Agency, personnal communication.

3. Princen, L. H., “New Crop Developments for Industrial

Oils,” The Journal of American Oil Chemists’ Society,

vol. 56, No. 9, 1979, pp. 845-858.

4. U.S. Department of Agriculture, 1980 Appraisal Part

II: Soil, Water, and Related Resources in the United

States; Analysis of Resource Trends, 1980.

5, U.S. Department of Agriculture, ERS, Agrictitural Statistics 1980.

6. U.S. Department of Agriculture, NRRC, estimate provided by industrial chemists located at the Northern

Regional Research Center, Peoria, 111., at the author’s

request, 1982.

7. U.S. Department of Agriculture, SEA, Developing a

USDA Program Toward Increasing Self Sufficiency in

Selected Strategic and Essential Industrial Materials.

A task force report prepared for the Director of the

Science and Education Administration, 1980.

8. U.S. Department of Agriculture and the Council on Environmental Quality, National Agricultural Lands

Study: Final Report, 1980.

9. U.S. International Trade Commission, Synthetic

Organic Chemicals USITC Publication 1001, 1979.
INFORMATION GATHERING AND DATA BASES THAT ARE PERTINENT

TO THE DEVELOPMENT OF PLANT-DERIVED DRUGS

Norman R. Farnsworth and William D. Loub*

College of Pharmacy

University of llIinois, Chicago

An important element of drug development using

plants is the accumulation and analysis of pertinent

research data and purported ethnomedical (folkloric) uses for plants. Due to the quantity of information frequently available in the literature and its appearance over many years from worldwide sources,

this information is best stored and analyzed by

computers, There are 10 automated data bases that

provide data on plant sciences, agriculture, and the

chemistry and pharmacology of natural products,

One of these data bases, the Natural Products Alert

(NAPRALERT) file, affords both bibliographic retrieval and textual and numeric data relevant to

drug development,

Status of lnterest in Drug

Development From Plants

A careful analysis of the National Prescription

Audit from 1952 through 1973 indicates that, contrary to general belief, the higher (flowering) plants

continue to provide useful, if not essential, drugs

for people of the United States and elsewhere (23).

The National Prescription Audit (NPA) collects

data on a monthly basis from a statistically significant number of community pharmacies throughout

the United States, These data include the number

of prescriptions dispensed, the trade mark or

generic name of the product prescribed, and the

price to the patient, Using these data and information on the origin of active principles (i.e., plantderived, microbial metabolizes, animal products,

mineral and/or pure synthetic), it is possible to determine which of the thousands of different prescription items included in the NPA contain active

principles extracted from higher plants.

From 1959-73, new and refilled prescriptions containing plant products represented 25 percent of all

prescriptions dispensed from community pharmacies in the United States. Over the survey period,

this percentage was never lower than 24 or higher

than 26 percent in any year. Incomplete analysis

of data for 1980 shows that plant-derived drugs still

represent approximately 25 percent of the total prescriptions dispensed.

*Presented at OTA workshop by N.R. Farnsworth,

178

Since the total number and average price of prescriptions sold annually at community pharmacies

are known, the value, at the consumer level, for

those prescriptions containing active principles

from higher plants can be calculated. However, it

is difficult to make the same calculation on the increasing number of prescriptions and quantity of

drugs dispensed from out- patient hospital pharmacies, extended care facilities, government hospitals, and other legitimate, but off-market, outlets

because data from these sources are not conveniently available. Nevertheless, in consultation with

academicians and others knowledgeable in pharmaceutical administration and economics, it was

determined that U.S. noncommunity pharmacy

prescription sales represent a dollar value almost

equivalent to that of drugs dispensed from community pharmacies. According to NPA data, 1.532

billion new and refilled prescriptions were dispensed from community pharmacies in the United

States in 1973. At an average cost to the consumer

of $4.13 per prescription, the dollar value for the

prescription market in 1973 was $6.327 billion.

Since 25.2 percent of the prescriptions contained

active principles of higher plant origin, the dollar

cost to the consumer in 1973 was $1.594 billion.

Adding almost an equal amount to this figure for

plant-derived drugs dispensed from other outlets,

an estimated total cost to the consumer was $3

billion in 1973.

Extrapolating from the 1959-73 data, and looking

at high-volume prescription drugs dispensed from

community pharmacies in 1980, the current annual

cost to the consumer is estimated to be in excess

of $8.116 billion,

NPA data for 1980 show that 41 species of higher

plants yield all of the plant-derived prescription

drugs. An additional 62 species of plants entered

the prescription market in the form of crude extracts with active principles. Less than 50 pure

compounds from plants were represented in the

prescriptions analyzed. The pure compounds, the

plants from which they are derived, and other

plants used in extract form in prescriptions are

listed in table 1.

Virtually all of the approximately 50 pure compounds used as prescription drugs (table 1) still are

produced commercially by extraction of plant material or by chemical modification of extracted plant

compounds. Although most of these drugs have
Information Gathering and Data Bases That Are Pertinent to the Development of Plant-Derived Drugs ● 179

Table 1 .—Flowering Plants That Currently (1980) Are Sources

of Useful Drug in the United States

Plant Names Family Type of Drug

Ammi majus

Ananas comosus

Atropa belladonna

——Avena sativa

Capsicum species (4)

Carica papaya

Cassia acutifolia

Cassia angustifolia

Catharanthus roseus

Cinchona species (3)

——Citrus limon

Colchicum autumnale

Digitalis lanata

Digitalis purpurea

Dioscorea species (several)

Duboisia myoporoides

Ephedra sinica

Glycine max

Papaver somniferum

Physostigma venenosum

Pilocarpus jaborandi

Plantago species (3)

Podophyllum peltatum

Prunus domestica

Rauvolfia serpentine

Rauvolfia vomitoria

Rhamnus purshiana

Rheum species (4)

Ricinus communis

—Veratrum viride—

Umbelliferae

Bromeliaceae

Solanaceae

Gramineae

Solanaceae

Caricaceae

Leguminosae

Leguminosae

Apocynaceae

Rubiaceae

Rutaceae

Liliacae

Scrophulariaceae

Scrophulariaceae

Dioscoreaceae

Solanaceae

Ephedraceae

Leguminosae

Papaveraceae

Leguminosae

Rutaceae

Plantaginaceae

Berberidaceae

Rosaceae

Apocynaceae

Apocynaceae

Rhamnacee

Polygonaceae

Euphorbiaceae

Liliaceae

Xanthotoxin a

Bromelain

Belladonna Extract

Oatmeal Concentrate

Capsicum Oleoresin

Papain

Sennosides A + B

Sennosides A + B

Leurocristine (vincristine)

Vincaleukoblastine (vinblastine)

Quinine

Quinine

Pectin

Colchicine

Digoxin

Lanatoside C

Acetyligitoxin

Digitoxin

Digitalis whole leaf

Diosgenin

Atropine

Hyoscyamine

Scopolamine

● Ephedrine

● Pseudoephedrine

Sitosterols

Opium

Codeine

Morphine

Noscapine

● Papaverine

Physostigmine (Eserine)

Pilocarpine

Psyllium husks

Podophyllin

Prune Concentrate

Reserpine

Alseroxylon Fraction

Powdered whole root Rauwolfia

Deserpidine

Reserpine

Rescinnamine

Cascara Bark

Casanthranol

Rhubarb Root

Castor Oil

Ricinoleic Acid

—Veratrum viride Extract —

Cryptennamine

aI.Underlined names indicate single chemical compounds of known structure.

● Also produced by synthesis
180 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

been synthesized, synthesis is not commercially

feasible, with the exception of a few drugs such as

ephedrine, pseudoephedrine, and papaverine.

In addition to the prescription drugs, the sale of

herbal teas in the United States is estimated at least

$200 million annually and the sale of over-thecounter (OTC) drugs obtained from plants is probably over $1 billion. For example, about one-half

of the OTC laxative preparations sold annually in

the United States are of plant origin. In 1980, exclusive of prescription sales, the laxative market

was about $331 million (an increase of 10.3 percent

over 1979). Data such as these are unavailable from

other countries, but a similar incidence of use is

likely in most of the developed countries.

One might presume that with a current market

value at the consumer level in excess of $8 billion

annually in the United States, most pharmaceutical

firms would have major research programs designed to discover new drugs from plants. This is

not the case. In 1974 the American pharmaceutical

industry’s total R&D budget for pharmaceuticals for

human use was $722.7 million. Only one firm was

involved in direct research to explore plants for

new drugs. At that time a conservative estimate

suggests that the annual research budget for that

single program was less than $150,000. Although

much has been written in scientific journals of this

country and abroad that should spark industrial interest to invest in this area of research, * interest

in this country has declined. Today there are no

U.S. pharmaceutical manufacturers involved in a

research program designed to discover new drugs

from higher plants.

Other developed countries generally have followed the United States pattern, with two major exceptions: West Germany and Japan. Exploration for

new plant-derived drugs in West Germany, however, has not captured the imagination of large

pharmaceutical firms. Instead, these studies are

supported by many small pharmaceutical manufacturers.

The Japanese situation is nothing short of phenomenal. Not only do Japanese academicians receive government and industrial support for research on plant drugs, but Japanese pharmaceutical

firms also have major research departments dedicated to the same goal. Scientific papers from

Japanese research laboratories relating to drugplant development generally are of high quality and

outnumber those from the United States by at least

tenfold. In addition, Japanese patents for plant-

*If none have been tested in humans yet.

derived biologically active substances outnumber

those from the United States by a factor of at least

50.

Factors Responsible for Decline of

Interest in Drug Plant Discovery

Important decisionmakers connected with drug

development apparently are unaware of the extent

to which plants contribute to our source of drugs.

During the past three or four decades, research administrators have been scientists trained and experienced primarily in synthetic organic chemistry,

biochemistry, molecular biology, microbiology,

medicine, or related fields. Plant sciences have not

had a voice in corporate or high-level governmental decisionmaking, except in the area of basic agriculture. Further, science has advanced to a point

where interest has not been on the intact organism—whether it be plant, animal, or microbe—but

rather on the cell, cell contents, and cell biochemistry. Typical industrial drug development increasingly has involved synthesis of molecules based on

structure-activity relationships, and natural product

drug development has been restricted to antibiotic

production by micro-organisms.

If drug development programs now are based on

synthesis and involve structure-activity relationships, what scientific process is available to identify plant-derived drugs? Most useful drugs derived

from higher plants have been “discovered” through

scientific inquiry into alleged folkloric claims of

therapeutic effects. The only other approach used

in recent years, although unsuccessful, has been the

random collection of plants followed by pharmacologic evaluation. This approach has been modified in several ways. For example, the Smith, Kline

and French Pharmaceutical Co. (SKF) had an extensive program for several years. SKF sent

workers into the field to carry out “spot tests” for

alkaloids on any plant that was reasonably abundant. Plants giving positive tests were collected in

1-to 5-kg amounts and sent to the parent research

laboratories in Philadelphia. The total alkaloid fraction was separated from each species and then subjected to a series of pharmacological tests. Nothing

has ever been published to provide an understanding of the rationale for the selection of pharmacological “screens” used in this program. The total

number of plants bioassayed was also unreported,

although they probably numbered several hundred

species. Many scientific reports came out of the

SKF studies, but they lacked pharmacologic information.
/formation Gathering and Data Bases That Are Pertinent to the Development of Plant-Derived Drugs ● 181

A major program of the National Cancer Institute

involving the “screening” of plants randomly collected worldwide ended in late 1981. This program,

which was started in about 1956, tested some

35,000 species of plants for antitumor activity in

laboratory animals. Although a large number of

highly active antitumor agents were discovered by

the NC I program, none have been approved for use

against human cancer by the Food and Drug Administration (FDA). A few remain to be studied in

humans. These* plant-derived antitumor agents

that appear promising and presumably will undergo eventual testing in humans are tripdiolide,

indicine-N-oxide, baccharin, isobaccharin, taxol,

10B-hydroxy with anolide, bruceantin, and homoharringtonine. The results of this program have

been reviewed through early 1982 (8,12,60,61).

One could argue that this approach of “blind”

screening any and all plants available in sufficient

quantity for testing is entirely unscientific and too

costly to be continued. Perhaps these are reasons

for the NCI’s canceling its program on antitumor

plants. Surely a program that fails to produce a

useful drug after 25 years of testing more than

35,000 species of plants must be examined to determine what went wrong!

Speaking in defense of the NCI screening program, Suffness and Douros (59) stated:

It is unfortunate that there has been a mutual

skepticism between theoretical researchers, who

are interested in a “rational” approach of discovering the biological differences between neoplastic

and normal cells in order to develop drugs, and the

approach of the empiricists, with the former group

feeling that the latter are using a hit or miss unscientific approach and the latter feeling the former

are divorced from the practical aspects of the problems. One hopes that this situation will progress

in such a way that the information gained by the

empiricists can be used to help the theorists develop new experimental methodologies and that the

theoretical information produced by the rationalists

can help the empiricists in their research. Structural analysis of new compounds developed

through an empirical approach has given us the basis to develop analogs of a compound which might

be beneficial and better than the parent active

compound.

With the amount of data now available from the

NCI antitumor plant program, it would be interesting and useful to conduct a scientific retrospective

analysis on data of all 35,000 species of plants tested

in this program,

A program at the Eli Lilly Co. * discovered two

useful antitumor drugs that still are widely used today. This program identified about 440 species of

plants for inclusion in a broad biological screening program, based on literature reports and recommendations of Dr. Gordon Svoboda. Catharanthyus

roseus, the Madagascar periwinkle, was the 40th

species bioassayed within the program and yielded

the useful antitumor agents leurocristine and vincaleukoblastine. From the discovery of the antitumor

activity of a crude extract of this plant, through the

isolation, biological testing, toxicity, and clinical

trials of vincaleukoblastine, less than 4 years were

required for FDA approval and the marketing of

this drug for the treatment of human cancer. The

second useful alkaloid, leurocristine, was marketed

2 years later.

Nothwithstanding the work on Catharantus, industry’s development of useful drugs from higher

plants during the past 30 years has not been more

productive than government efforts. Since 1950,

pharmaceutical companies have produced only

three plant-derived drugs that have reached the

U.S. prescription market: reserpine (and the related

deserpidine and rescinnamine), vincaleukoblastine,

and leurocristine. The total number of industry research dollars required to discover these drugs has

been miniscule compared with the cost of placing

synthetic drugs on the market. If industry invests

next to nothing in drug-plant development, what

can it expect in the way of marketable compounds?

Perhaps a major deterrent to industrial interest

in plant drug development is that much of the unexplored flora of the world currently is found in

tropical and/or semitropical areas, especially in

developing countries. Because many of the countries’ governments are considered to be unstable,

an uninterrupted supply of raw material for manufacture of a new drug developed from a plant indigenous to such areas may not always be assured.

This seems a weak argument to justify the lack of

plant drug development, since rarely is a plant

found only in one country. In addition, alternate

sources of supply, including cultivation, always

should be developed when a useful drug is discovered.

Some companies feel that patent protection is less

secure with natural products than with synthetics.

We have not been able to document examples supporting this contention. To the contrary, there is

no evidence that the Eli Lilly Co, experienced difficulties with patents assigned to them for the anti-

*(5), (111, (14), (15), (16), (17), (18), (19), (20), (23), (24),

(54), (55). *See paper by Svoboda in this volume.
182 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

tumor alkaloids vinceleukoblastine and leurocristine, whose annual worldwide sales are $50 million

at the manufacturer’s level.

Information That Should Be Included

in Data Base Useful for Drug

DeveIopment From Plants

A data base that would be useful in a program

of drug development from plants should include the

following information:

The Plant

Information on the plant should include: its most

current Latin binomial and all recently employed

botanical synonyms, along with the authority, varieties, subspecies and lower taxonomic groups, the

family name of the plant, and vernacular (common)

names; the geographic area where the plant was

collected and all known areas where the plant occurs naturally or under cultivation; whether or not

a voucher specimen representing the investigated

material was prepared and stored; and the part(s)

of the plant studied.

Ethanomedical Uses

Documentation of the crude plant material (fresh,

dried, pulverized) or type of extract employed in

preparing the ethnomedical dosage form, route of

administration, dose employed, dosage regimen,

side effects, and beneficial effects claimed should

be retrievable from the database. The ethnomedical

claim(s) should also be computerized to allow for

retrieval of information on analysis of related effects. For example, a plant extract maybe alleged

to be useful as an ethnomedical preparation for arthritis and/or rheumatism. Experimental data may

have been reported elsewhere indicating that an extract of the same plant has shown anti-inflammatory activity in vivo and in vitro. It may also have

been reported to have analgesic activity and to inhibit prostaglandin synthetase in vitro. These experimental pharmacologic effects suggest that the

extract could be beneficial in treating arthritis

and/or rheumatism. Ideally, a data base useful for

drug development would have the capability of relating general ethnomedical information with experimental data to predict useful drug effects.

Chemical Constituents of Plants

It is important to be able to retrieve data on the

chemical constituents of plants, the part of the plant

in which the constituent is reported to be present,

the range of percentage yield of the chemical, and

any available data on seasonal or other variations

in chemical quality or quantity.

If a chemical compound is known to produce a

pharmacologic effect, the presence of such a compound in the plant may explain either the experimental pharmacology of an extract of the plant or

an ethnomedical claim relating to the effect of the

known chemical constituent. An appropriate computer analysis relating ethnomedical claims, experimental pharmacology of plant extracts, occurrence of chemical constituents, and pharmacological effects of naturally occurring chemical constituents may indicate that all aspects of a given problem have been studied, even though the answer is

scattered in several publications from different

parts of the world. Such computer analysis can prevent costly and time-consuming redundant research. Sources of all data should be coded and

specifically linked for subsequent retrieval and reevaluation or reinterpretation as may be necessary.

Additional valuable information in a data base is

classification of various naturally occurring chemical compounds by general class, sub-structure, and

functional groups on the molecule. Computer analysis of a series of plant-derived chemical constituents with regard to chemical structure biological

effects could be useful in the advanced stages of

drug development.

Experimental Biological Testing

For Plant Extracts. It is important to be able to

identify the type of solvent used to prepare an extract of a plant tested for biological activity, since,

for example, an extract using petroleum ether

would be expected to react differently than one prepared with ethanol. Further, the type of biological

test—i.e., in vitro, in vivo, or human study—is important, since the credibility of data with respect

to its ultimate value as a drug would be of the order

in vitro < in vivo < human study.

A system for identifying similar and related biological effects would be required if computer analysis of the data is anticipated. Thus, central nervous system, autonomic, hematologic, chemotherapeutic, and/or hormonal effects, etc. should be

organized so they can be retrieved and analyzed as

a group or for a specific effect within each group.

Test species should be identifiable, since data using

rodents, for example, may not be as significant as

data derived from primate studies. The route of administration is important, as is the dose, dosing

scheduled, and qualitative and/or quantitative
Information Gathering and Data Bases That Are Pertinent to the Development of Plant-Derived Drugs . 183

result. The disease states of animal models or the

type of experimental model also should be documented.

For Pure Compounds. All of the above

parameters should be documented for test results

on plant chemical constituents, with the obvious

exception that the type extract would not apply.

Other Important Information

It would be of interest in any plant-derived drug

development program to be able to retrieve references to naturally occurring chemical compounds

that have been partially or completely synthesized.

Similarly, data relating studies on the cultivation

of useful drug plants and the effects of cultivation

conditions, processing, and storage on the yield of

useful active constituents would be useful in a data

base for drug-development purposes.

Eventually plant-derived drugs probably will be

produced by cell culture, although the necessary

technology is not so advanced that commercial applications of tissue culture for this purpose will be

available soon. Little work is being supported either

by industry or government in the United States to

develop plant tissue culture for this practical application.

Similarly, genetic engineering some day may be

applied to producing plant-derived drugs. However, the production of useful drugs by plants is

always a multistage process. Transfer of several sets

of genes to microbes would be required to produce

secondary metabolizes that are useful drugs. We do

not know of any current efforts in this area. Most

likely a detailed examination of the biosynthesis of

the drug that would be a candidate for production

by genetic engineering would have to be carried out

in each case, Again, basic studies that would provide this type of information are not being supported to any extent in this country,

Accessibility of Data Pertinent to

Plant-Derived Development

Data of value in organizing and implementing an

effective plant-derived drug development program

are difficult to obtain through currently available

on-line data bases. Further, much of the useful

pharmacologic data on plant extracts was published prior to the earliest data covered by all of the

available online data bases. Also, the format in

which data can be retrieved from most available

systems is inadequate for practical use in a major

program.

It has been our experience that the pharmaceutical companies are reluctant to share data derived

from testing plant extracts, even if the data are

negative and are of no commercial interest to the

firms, In the United States alone, some pharmacological data on perhaps several thousand species

of plants have been documented by industrial firms,

but remain unpublished. Negative data are as important as positive data in a broad plant-based drug

development program, and it is unfortunate that

some mechanism cannot be found to persuade industrial firms to make their unpublished in-house

pharmacologic data on plants available to the general scientific community.

The National Cancer Institute published negative

data regularly at the beginning of the plant screening program. This apparently became an expensive

exercise because most of the data now remain unpublished. If one requests information on a few

species of plants, NC I will provide the information

from its files, but probably would not supply large

amounts of data.

If one examines the format for the initial negative

data published by NCI on testing plants for antitumor activity, it is obvious that much of the spaceconsuming information was superfluous-i. e., one

line of data for each dose level tested. Since all the

data are computerized, NCI should be encouraged

to produce several volumes of negative data, allowing only one line per species with similar testing

conditions. An entry of data would then appear as

follows: Genus-Species-Authority-Family-Country

Where Collected-Part-Tumor System. Such a list

of negative data would be of enormous interest to

scientists throughout the world and would help

them in selecting new plants for study without duplicating past work.

A similar problem exists with obtaining large

amounts of useful data from published reports. For

example, there are several hundred literature reports in which large numbers of plants have been

screened for one to at least thirty biological effects.

The names of plants in these multiple-entry reports

rarely are obtainable from the subject indices of

Chemical Abstracts or Biological Abstracts, a n d

presumably from data bases using these sources.

Steps Involved in Gathering

Information and Implementing a

Plant Drug Development Progam

Diczfalusy (11) has discussed the general steps in

developing drugs of plant origin. After the initial

decision is made concerning how candidate plants
184 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

are to be selected for investigation, procedures to

be followed are reasonably straightforward (see

table 2).

Information Gathering

Suffness and Douros (59) have given their views

on the relative advantages of using folkloric information, botanical relationship, and random collection approaches to identifying plants for inclusion

in the NCI screening program (see table 3). If the

plants to be screened are not chosen randomly, they

should be chosen on the basis of available information.

Information-gathering to identify candidate

plants for study will vary considerably, but most

likely will necessitate searching for data in the

following areas.

Ethnomedical data. Ethnomedical (folkloric) information on plants is not indexed or abstracted in

any organized way. Sources include books on medical botany, review articles, floras of various geographic areas, pharmacopoeias of different countries, anthropological writings, folkloric writings,

and popular books on uses of plants. No one can

be reasonably certain that all data collected for a

given plant or for a biological effect of interest have

been acquired from ethnomedical reports. To the

best of our knowledge, only the USDA data base*

and our NAPRALERT system (to be described sub-

*See paper by Duke in this volume.

Table 2.—Selection of Approachs for Drug Development From Plantsa

Method of Selection Advantages Disadvantages

L Folklore Use

2. Botanical Relationship

3. Random Collection

High ratio of activity

Lower screening costs

High ratio of activity a n d

Discovery of useful

analogs

Best chance to find novel

active compounds

Plants are more readily

available

Role of psychology in folk

medicine

Secrecy of primitive cultures

Difficulty of botanical

identification

Use of complex plant mixtures

Use of rare plants

High procurement costs

Leads may be missed

Limited amount of screening

possible

Lack of novel active compounds

Reisolation of known compounds

Low percentage of active leads

Large bioassay capacity needed

High cost per lead

aModified from Suf fness ~d Douros (1979)0
Information Gathering and Data Bases That Are Pertinent to the Development of Plant-Derived Drugs Ž 185

Table 3.—Steps Required for Drug Development From Plants

1 .

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

Decision on method to select plants

Preparation of extracts for bioassay.

Initial collection and identification of plants

Bioassay of plants

Recollection of active plants for confirmation of activity

Fractionation of active plants following bioassay.

Isolation of active compound(s) in sufficient quantity for bioassay and

identification or structure elucidation

Determination of pharmacologic profile for active compound(s)

Acute and chronic toxicity studies

Large scale preparation of the active compound(s)

a. Large scale procurement of active plant

b. Pilot plant scale development of efficient isolation procedures

Initiate studies designed to prepare the active compound by complete

to prepare active analogs

Formulation studies

Pharmacokinetic and metabolism studies

synthesis and

File an Investigational New Drug Application (INDA) with the Food and Drug

Administration

Phase

Phase

Phase

File a

I human studies

11 human studies

HI-IV human studies

New Drug Application (NDA) with the “Fred and Drug Administration

Market the new dru g

sequently) contain retrievable ethnomedical information. Some people discount the value of folkloric

reports of medical efficacy of plants, but in doing

so refute the historical documentation of how such

information was used in the discovery of such major drugs as digitoxin, reserpine, tubocurarine quinine, codeine, morphine, and others, The degree

to which one uses ethnomedical information will

vary according to the background, training, and

capabilities of scientists involved in a drug-development program.

Experimental Data on Plants. The subject indices of several abstracting services usually identify plants tested for biological effects or plants from

which chemical compounds have been obtained.

We routinely use those abstracting services listed

in table 4, which identify the period and type of

literature covered in each case.

A word of caution has to be given, however. We

have found less information on plants in decennial

indices of Chemical Abstracts when compared to

annual indices. We have also found that a great deal

24-503 0 - 83 - 13
186 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Table 4.-Secondary Literature Indices Used in the NAPRALERT Program

Title Period Covered

INDEX CATALOG OF THE SURGEON GENERAL 1880-1961

INDEX MEDICUS 1897- 1927; 1960 to present

CHEMICAL ABSTRACTS 1907 to present

QUARTERLY CUMULATIVE INDEX MEDICUS 1916-1956

BIOLOGICAL ABSTRACTS 1926 to present

CURRENT LIST OF MEDICAL Literature 1941-1959

UNITED STATES ARMED FORCES MEDICAL JOURNAL 1950-1960

NATIONAL LIBRARY OF MEDICINE CATALOG 1956-1965

NATIONAL LIBRARY OF MEDICINE CURRENT CATALOG, 1966 to present

CUMULATIVE LISTING

CURRENT CONTENTS, LIFE SCIENCES 1967 to present

of useful information, especially concerning pharmacological effects of plant extracts, is found in

earlier abstracting services (i.e., those indicated in

table 4 that cover periods prior to 1907). We also

routinely check the bibliographies of pertinent articles, especially review articles, on subjects of concern to the area of the chemistry and pharmacology

of specific plants and/or specific pharmacologic effects and find a significant number of useful papers

that were not identified through systematic literature searches of the services indicated in table 4.

If current work indicates that one or more research groups throughout the world are publishing

extensively in an area of interest, correspondence

with those groups usually uncovers additional literature that is not usually available through indexing services.

Finally, the use of one or more of the online computer data bases to acquire citations and/or abstracts on a particular subject may be advisable.

In our laboratory, experimental work on a plant

does not commence until we have acquired all of

the ethnomedical and scientific literature available

through the aforementioned means, including data

on taxa closely related to the plant of interest.

Plant Collection. It has been our experience that

although botanists are essential to the success of

plant-derived drug development programs, they are

the most unappreciated of the scientists involved

in such a program. The botanist can not only clarify

nomenclatural problems but has the credentials to

contact other botanists in countries where the

plants of interest grow. The botanist can provide

sources of background information that would be

unknown to the chemist and/or pharmacologist.

Often this information is critical to a project’s success. Through field work, the botanist can clarify

vague points found in the literature on which several varieties of a species should be collected and

can gather additional information from users of

plants in the area where collections are to be made.

These data may be useful to the pharmacologist on

a drug development team in designing an animal

study to assess the biological effects of a plant.

A number of government regulations pertaining

to plant importation must be considered. For ex-
Information Gathering and Data Bases That Are Pertinent to the Development of Plant-Derived Drugs . 187

ample, depending on the method used, fumigation

of a plant entering the United States could produce

chemical changes in the plant, rendering the chemical constituents inactive. The botanist can maintain communication with government botanists at

points where plants enter the country and often can

prevent such problems.

Bioassay Procedures. A critical stage in drug

development from plants is the selection and implementation of bioassay procedures and interpretation of their results. Few pharmacologists are experienced in evaluating crude plant extracts or are

interested in developing bioassay systems outside

their own area of interest, In a large program,

where several pharmacologists can become involved, “specialization” may be possible. However,

even though a program is designed to identify only

one or two types of biological activity, it would be

cost ineffective not to carry out as many bioassays

as possible, since the expense of acquiring the plant

may be quite high.

Because there is inherent variation in laboratory

animal experimentation, drug development programs involving plants should include a series of

so-called in vitro “pre-screens. ” Plants should be

selected on the basis of having predictive activity

in animals and/or humans. Examples of some in

vitro bioassays used for plant extracts are presented

in table 5. If initial in vitro activity seems promising, in vivo activity can be confirmed in laboratory

animals. Alternatively, isolation of the compound

responsible for the activity can be accomplished

using bioassay-directed fractionation with simple,

rapid, and less expensive in vitro tests. The pure

compound then can be tested in laboratory animals.

Many ubiquitous chemical compounds found in

plants elicit biological effects but have no practical

use as drugs, It would be important to identify such

compounds, carry out a simple chemical test to indicate the presence of the compound in plants to

be bioassayed, then modify experiments to rule out

the effect of the undesired ubiquitous compound.

Isolation and Identification of Biologically Active Principles From Plants. Presuming that the

goal of a drug development program is to develop

pharmaceuticals, it is first necessary to establish a

biological effect for a plant, then isolate the compound(s) responsible for the effect by bioassay-directed fractionation. Some biological activity may

not be detected by means of a simple and rapid in

vitro bioassay, thus presenting a major problem. If,

however, the desired biological activity can be demonstrated in a laboratory animal after one or two

doses, the in vivo bioassay can be used as an aid

to fractionation. It is most useful to have bioassay

capability in-house rather than to rely on outside

chemical work.

Routine techniques are available for isolation and

purification of the active principle(s) after one has

fractionated a plant so that biological activity has

been enriched severalfold. Column chromatography, ion-exchange, droplet counter-current chromatography, and high performance liquid chromatography are some well-established techniques.

However, if the active compound is to be developed

into a marketable item, a practical means for isolating it from the plant must be found, Few compounds exist that could be separated economically

from plants by chromatographic techniques and

every effort should be made to use simplified

procedures.

Once the active principle has been obtained in

pure form, identification is routine if it is a known

substance. In cases of novel compounds, methods

are available to determine the structures in a

relatively short period of time, providing that

modern instrumentation is available, including

pmr, cmr, ms, and X-ray crystallography equipment.

Clinical Evaluation and Marketing. Any drug

development program, whether it is industrial,

academic, or governmental, must at some period

involve the partnership of an industrial firm.

Academia and Government usually do not have the

capability to market a drug, but industry has the

experience and know-how. Clinical evaluation is an

expensive and complicated process, and is possible in the United States only after filing an investigational New Drug Application (INDA) with the

Food and Drug Administration (FDA). If approved,

human experimentation within certain guidelines

is allowed. Prior to marketing a drug, a New Drug

Application (NDA) must be filed with FDA, providing all data from the results of Phase I-IV human

studies allowed by the INDA, The drug, if approved, may then be marketed. The estimated cost

for developing a drug varies depending on the

clinical applications, but would not be less than $5

million and could be as high as $35 million per new

drug.

Data Bases Pertinent to

Drug Plant Development

There are about 1,000 online data bases—i.e.,

those searchable by the user from various types of

terminals (10,27,66). Ten data bases seem to have

information useful to a plant-derived drug develop-
Table 5.—Examples of in vitro Bioassays That Are predictive for UsefuI Drug Effects or Improvement of Health

Type Assay Type System Implied Useful Effect Reference

. .

Antiviral cell culture

ATPase inhibition in vitro

Benzpyrene hydroxylase (AHH) inhibition in vitro

Cell transformation cell culture

Cytotoxicity cell culture

Free radicals in vitro; cell culture

HMG-COA reductase inhibition in vitro

Human stem cell assay cell culture

Adenosine deaminase inhibition in vitro Enhancement of drug efficacy

Angiotensin-converting enzyme Inhibition in vitro Antihypertensive

Antibacterial activity bacterial culture Anti infective

Antifungal activity fungal culture Antiinfective

Antimitotic activity cell culture Anticancer

Antimutagenic activity cell culture or bacterial culture Anticancer

Anti Infective, anticancer

Cardiotonic

Carcinogenesis inhibition

Carcinogenicity detection

Anticancer

Anticancer

Antihypercholesterolemic, antiatherosclerotic

Anticancer

Kalckar, 1947

Yun, Chung & Han, 1981

Farnsworth, et al., 1966

Mitscher, et al., 1972

Farnsworth, et al., 1966

Mitscher, et al., 1972

Suffness & Douros, 1982

Abbott, 1980 bade, et al., 1981

Calle & Sullivan, 1982

Katak, et Q., 1980

Stich, Rosen & Bryson, 1982

Wood, et al., 1982

Farnsworth, et al., 1966

Markkanen, et al., 1981

Barnett, 1970; Chen, et Q., 1982

Duggan & Nell, 1965

Pezzuto, et al., 1978

Merriman & Bertram, 1979

Nescow & Heidelberger, 1976

Suffness & Douros, 1982

Germ, et al.,

Sarriff, White & DiVito, 1979

Tappel; 1972

Stacpoole, Varnado &

Salmon, et al., 1978

VonHoff, et al., 1981

Island, 1982

a ~ -Hydroxy-8 -methylglutaryl COA reductase
Information Gathering and Data Bases That Are Pertinent to the Development of Plant-Derived Drugs . 189
190 Ž Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

ment program. Nine of these are summarized in

table 6, the tenth is developed at the USDA by Dr.

James Duke.* We are unaware of data bases that

contain information pertinent to plant-derived drug

development in the People’s Republic of China,

Japan, or the U.S.S.R.

AGRICOLA (formerly CAIN). This database is

produced by USDA but is available through commercial vendors such as BRS, DIALOG, and others.

It covers the literature from 1970 to the present on

agricultural chemistry and engineering, food and

plant science, nutrition, and related agricultural

fields. Approximately 6,500 journals are reviewed

for input. The bibliographic file is composed of 90

percent journal articles and 10 percent monographs, published proceedings, and/or theses, Subject analysis by the user is carried out using controlled keywords-i. e., those provided in a prepared

thesaurus or through enriched titles. Chemical

identifiers include the use of nomenclature codes,

fragmentation schemes, or the chemical name as

it appears in the source of data.

BIOSIS PREVIEWS. This file has been produced

by Biosciences Information Services and is also

available through commercial vendors. Its subject

matter includes life science data for microbiology,

the plant and animal sciences, experimental medicine, agriculture, pharmacology, ecology, biochemistry, and biophysics. A search of the file provides

bibliographic data for information obtained from

approximately 94 percent journal articles, less than

1 percent government documents, and the remainder from monographs, published proceedings, or

theses. Search methods include the use of enriched

titles, uncontrolled keywords (i.e., keywords selected by the user and not from a prepared thesaurus), and subject headings that may appear in the

title. Chemical identification uses the same type information described above (see AGRICOLA).

CAB SYSTEM. The Commonwealth Agricultural

Bureau System of England produces this file, which

is also available in the United States. The CAB System has bibliographic data and abstracts obtained

from a review of approximately 8,000 journal titles

covering the literature from 1973 on. It represents

a compilation of 20 agricultural science databases,

and includes subjects such as animal and plant

breeding abstracts, plant pathology, nutrition, entomology, and related fields. Searching this database requires the use of uncontrolled keywords and

subject titles.

*See paper by Duke in this volume.

FSTA. This is an acronym for Food Sciences and

Technology Abstracts. Its subjects include agricultural chemistry and engineering, food science,

home economics, and patents from approximately

1,300 journal titles. The resulting database is composed of 85 percent journal articles, 10 percent patent information, and 5 percent monograph, government document, or theses data. Search techniques use uncontrolled keywords and/or enriched

titles. Chemical compounds again are identified

using registry codes, fragmentation schemes, or the

name which appears in the document processed.

All data are bibliographic with abstract summaries

for the years 1969 to the present,

CACON (Chemical Abstracts Condensate).

CACON is one of the largest and most widely distributed bibliographic databases in the world. This

file is a product of Chemical Abstract Services and

covers most life sciences and physical sciences

from 1968 on. Literature coverage includes input

from approximately 14,000 journal titles and results

in a computerized file made up of 72 percent journal articles; 2 percent government documents; 10

percent monographs, published proceedings, or

theses; and 16 percent patent information. Subject

retrieval is carried out using uncontrolled keywords, which may appear in the article title or its

abstract, subject headings, and/or word strings. The

latter are searched in the computerized abstract

material.

MEDLINE. This file, produced by the National

Library of Medicine (NLM), covers the literature

from 1974 on. Depending on the literature period

of interest, it is offered either on-line or off-line. Input data are obtained from approximately 3,000

journals titles comprising life sciences and/or medical information. These data are represented in the

file by 99 percent journal articles, of which 65 percent are in the English language. The remaining 1

percent of data represents government documents.

Retrieval provides bibliographic data with an

abstract summary and is obtained by using keywords and/or subject headings.

IMEPLAM. This is the acronym for Instituto

Mexicano Para el Estudio de las Plantas Medicinales (Mexican Institute for the Study of Medicinal

Plants). Data contained in this data base have been

derived from 41 literature citations primarily concerned with collections of natural history and folkloric claims for Mexican plants. These volumes,

which have been computerized, date from 1552 to

1973, We have not been able to document whether

current literature is being added to these data. Its

primary value is with regard to ethnomedical data
Table &-Major Computerized Sources of Scientific and Technical information on Natural Products

DATA BASE NAME LITERATURE TYPE DATA NUMBER OF SCOPE OF COVERAGE

(ACRONYM) COVERAGE RETRIEVABLE JOURNAL TITLES

(from) REVIEWED

AGRICOLA

(formerly CAIN)

BIOSIS Previews

CAB System

FSTA

(Food Sci. & Tech. Abstr.)

CA SEARCH

MEDLINE

IMEPLAM

Chinese University

of Hong Kong

NAPRALERT

(Natural Products Alert)

1970

1969

1973

1969

1978

1974

(a)

1975 (d)

Literature

citations

Literature

citations

Literature

citations + Abstr.

Literatue

citations + Abstr.-

summary

Literature

citations

Literature

citations + Abstr.

summary

Literature

citations + Plant

use data (b)

Literature

citations + Abstr.

summary

Literature

citations + tabular

numerical and textual

data from article

6,500

8,000

8,000

1,300

14,000

3,000

41 (c)

8,000

Agricultural chemistry and engineering; food and plant

science; nutritional data, etc.

Life sciences; microbiology; plant and animal sciences;

experimental medicine; agriculture; pharmacology; ecology;

biochemistry; biophysics.

Agricultural science; plant and animal breeding; plant

pathology, nutrition; entomology.

Agricultural chemistry and engineering; food science;

economics; patents.

Life sciences; physical sciences

Life sciences; medical information

Clinical and folklore use; type pharmacological testing;

Mexican plants only.

Retrospect and current information on Chinese Traditional

medical practices.

Plant, microbial and animal (primarily marine) chemistry

and pharmacology; folkLore.

(a). Retrospect information obtained from reference materials and books covering periods from 1552 through 1973.

(b.) Categorical data only no numerical or textual information.

(c.) Fixed bibliography. No indication of current awareness data entry.

(d.) Also includes retrospect data on more than 500 genera of plants extending into the mid-1800’s.
192 • Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

systematically presented for a significant number

of Mexican plants. Pharmacological testing data in

the file are not presented in detail.

Chinese University of Hong Kong. This data

base is purported to contain both retrospect and

current literature citations as well as brief abstracts

of Chinese publications on traditional medical practices. The availability of this data base in the United

States has not been established. Nevertheless, the

systematic and well organized approach of traditional Chinese medicine makes this data base worth

listing as an adjunct to any program for drug development from plants.

Although the literature coverage of these combined databases is quite comprehensive, the inability to compare, correlate, or analyze research data

analytically—since they are bibliographic in nature—is a serious drawback of using the data bases

in drug or new product development. These data

bases provide only lists of citations within the specificity of the search terms—i. e., keyword and/or

phrases. If one attempts to be too specific, many

citations are overlooked because such specific

terms are not used in titles or summary abstracts.

On the other hand, broad descriptions within the

search terms provide many citations that are not

pertinent to new product development research.

Ideally, one would desire a nonbibliographic file

that could list and, by computer, compare or correlate real data contained in pertinent citations,

then present the data in a digestible tabular form

and provide the citation sources. Such nonbibliograhic data files on natural products are not available on-line to the best of our knowledge.

Such a data base does exist off-line. In 1975,

NAPRALERT, the acronym for Natural Products

Alert, was conceived as a program to overcome the

difficulties in using existing files for developing

research projects associated with natural products

and drug development.

NAPRALERT Content. NAPRALERT, representing a survey of the world literature on natural

products, was started in 1975 through a systematic

review of each issue of Chemical Abstracts a n d

Biological Abstracts. Since that time, a large

number of retrospect literature searches have been

carried out on organisms or subjects of special interest. These retrospect searches cover the literature from the mid 1800’s or early 1900’s to the present. Approximately one-third of the citations now

computerized in NAPRALERT represent these retrospect data. The NAPRALERT database contains

information from about 65,000 research reports,

books, reviews, patents, and dissertations.

a. NAPRALERT Data Types. In addition to bibliographic information, NAPRALERT records the

chemical constituents and pharmacological bioassay information from plant, microbial, and animal (primarily marine) extracts. The accepted and

synonymous nomenclature of the organism, the

parts of the organism used in the study, and the

geographic source of the material are also important elements of the data base. In addition to published data, many different indicator codes are used

to alert the user that literature is available on the

subject or to perform unique sorting capabilities.

Another unique, but useful, parameter of the

NAPRALERT file, is the recording of ethnomedical, or folkloric, notes as they are encountered in

the literature. As a single bit of information, such

claims may be of doubtful value, but when correlated with known pharmacologic data or chemical

constituents, such data can provide interesting relationships to rationalize the plant’s investigation.

b. NAPRALERT Application. Two especially

important applications of this data base are related

to identifying potential sources of useful new products. First, random screening of plants can be

systematized by an organized computer search and

analysis of data to provide a ranked list of the more

probable candidates for study prior to any field efforts. Such a methodology was developed using

NAPRALERT and was tested for a WHO Task

Force assembled to identify indigenous plants potentially useful for human fertility regulation.

In this instance, approximately 4,500 plants were

identified as purported to affect fertility, based on

folkloric claims or laboratory experiments. To select plants randomly for laboratory investigation

from a list this size would not be feasible or cost

efficient. Thus it was decided to use the pharmacological data, folklore information, and geographic

data contained in the NAPRALERT database as a

means of identifying the most promising plants for

initial study. After developing appropriate software

and subsequently analyzing NAPRALERT-contained data, approximately 300 plants from the list

of more than 4,500 were identified as the most

promising for study. To date, 50 of these have

received preliminary laboratory investigation and

eight have confirmed activity using two different

laboratory animal assays. Although successful development of a useful clinical drug has not been

achieved yet, it seems that such a predictive analysis of appropriate computerized data can be a valuable adjunct to new drug development. In this instance, a list of plants with a predictable area of

biological activity was generated by evaluation of
Information Gathering and Data Bases That Are Pertinent to the Development of Plant-Derived Drugs ● 193

the non-bibliographic computerized research data

rather than by a costly and time-consuming random

field screening process. Certain aspects of the

WHO-supported practical application of the

NAPRALERT data base have been published

(22,54).

A second important application of the information contained in the NAPRALERT file is the ability

to present within one computerized report all published folklore information, biological activities—

whether assayed in vitro, in animals, or in humans—toxicities, and chemical constituents. In this

form, these data can be used effectively to assess

potential dangers or suggest safeguards which

should be employed when using certain plants.

These same data may suggest areas for research on

new uses or applications of a specified plant or

group of plants. To envision such results only from

a stack of publications can be a formidable and frustrating alternative approach.

Acknowledgments

The National Prescription Audit (NPA) used in

calculating certain data presented in this manuscript was kindly provided through the courtesy of

IMS America, Ltd., Ambler, Pa.

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38. Munakata, K., and Wada, K., “Insect Antifeedants in

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39. Nikaido, T,, Ohmoto, T., Noguchi, H., Saitoh, H., and

U. Sankawa, “Inhibitors of Cyclic AMP Phosphodiesterase in Medical Plants,” Planta Med., vol. 43,

1981, pp. 18-23.

40. Ohkoshi, M., “Inhibition of Growth of 3-Methylcholanthrene-Induced Mouse Skin Tumor by Protease Inhibitor (N, N-Dimethylcarbamoylmethyl-4-(4-

Guanidinobenzoyloxy)-Phenylacetate) Methanesulfate,” Gann, vol. 72, 1981, pp. 959-965.

41. Ohuchi, K., Kamada, Y., Levine, L., and Tsurufuji, S.,

“Glycyrrhizin Inhibits Prostaglandin E2 Production

by Activated Peritoneal Macrophages From Rats,”

Prostaglandins Med., vol. 7P 1981, pp. 457-463.

42. O’Neill, J. P., Brimer, P. A., Machanoff, R., Hirch, G.

P., and Hsie, A. W., “A Quantitative Assay of Mutation Induction at the Hypoxanthine-Quanine Phosphorobiosyl Transferase Locus in Chinese Hamster

Ovary Cell (CH)/HGPRT System): Development and

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43, Perry, P,, and Evans, H. J., “Cvtolo~ical Detection of

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Mutagen-Carcinogen Exposure by Sister Chromatid

Exchange,” Nature (London), vol. 258, 1975, pp.

121-125,

Pezzuto, J. M. and Hecht, S. M., “Amino Acid Substitutions in Protein Biosynthesis Poly A-Directed

Polyphenykdanine Synthesis,” J. Bio]. Chem., vol. 255,

1980, pp. 865-869.

Pezzuto, J. M., Moore, P. D., and Hecht, S, M.,

“Metabolic Activation of 3-Amino-l-Methyl-5 H-Pyrido(4,3-b)-Indole and Several Structurally Related

Mutagens,” Biochemistry, vol. 20, 1981, pp. 298-305.

Pezzuto, J, M., Yang, C. S,, Kang, S. K., McCourt, D.

W., and Gelboin, H. J., “Metabolism of Benzo(a)Pryene and (-)-trans-7,8-Dihydroxy-7,8-Dihydrobenzo(a)

Pyrene by Rat Liver Nuclei and Microsomes,” Cancer

Res., vol. 38, 1978, pp. 1241-1245.

Phillipson, J. D., “Chemical Investigations of Herbarium Material for Alkaloids,” Photochemistry, vol.

21, 1982, j)p, 2441-2456.

Robinson, D., Lovenberg, S., W., Keiser, H., and A.

Sjaerdsma, “Effects of Drugs on Human Blood Platelet and Plasma Amine Oxidase Activity in vitro and

in vivo, ” Biochem. Parmacol., vol. 17, 1968, pp.

109-119.

Saeed, S. A., Butt, N. M., McDonald-Gibson, W, J.,
Information Gathering and Data Bases That Are Pertinent to the Development of Plant-Derived Drugs • 195

50.

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and Collier, H. O. J., “Inhibitor(s) of Prostaglandin

Biosynthesis in Extracts of Oat (Avenasativa) Seeds,”

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Salmon, S. E., Hamburger, A. W,, Soehnlen, B., Durie,

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Cells to Anticancer Drugs,” IV. EngZ. J. Med., vol. 298,

1978, pp. 1321-1327,

Sarriff, A. M., White, W. E., and Divito, N., “Establishment of Phot-affinity Label Derivatives of

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VOI, 39, 1979, pp. 3903-3908.

Sedwick, W. D., Shu-Pong Wang, R., and Kern, D.,

“The DNA Polymerases of KB Cells,” A4ethods Ensymol., vol. 29, 1974, pp. 89-102.

Sirica, A. E., Huang, C. G., Sattler, G. L,, and Pitot,

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1981, pp. 66-69.
THE USDA ECONOMIC BOTANY LABORATORY’S

DATA BASE ON MINOR ECONOMIC PLANT SPECIES

James Duke

U.S. Department of Agriculture, Beltsville, Md.

The world is fed mainly by a dozen plant species,

and most agricultural countries have specialists for

their country’s major crops. The world also has

thousands of minor economic species, which potentially are as important ecologically and economically as the big dozen, but there are not enough

specialists to study them. There is an overwhelming number of climatological, pedological, anthropological, latitudinal, and biological variables

associated with these minor species. The Economic

Botany Laboratory (EBL) of the U.S. Department

of Agriculture (USDA) is trying to gather data on

these potentially economically useful species.

In 1971, USDA asked me to develop an information system on potential alternative crops for narcotics. With no computers available, I set up a manual information retrieval system of transparencies

for screening 1,000 economic plants as potential

substitutes. In 1972, I was encouraged to abandon

the transparencies for computers. Now, 10 years

later, there are many data in the computer. However, the computer bill for 1981 was over $50,000,

and with the loss of our support from the National

Cancer Institute, we can no longer afford to keep

the data bases online.

Data Base Files and Subsets

Some of our files and their subsets are listed

below, subjectively ranked in decreasing order of

importance to USDA’s Beltsville Agricultural Research Center.

1. ECOSYSTEMATICS

Germ Plasm Donor Subset (mailing list)

Monthly Temperature

Monthly Precipitation

Soil pH

Soil Type [limited)

Salinity (more limited)

Tolerances (not computerized)

2. YIELD

Phytomass Subset

Cultural Subsets

3. CLIMATE

Wernstedt

Questionnaires

Publishing Experiment Stations

4. NUTRITION

Food Composition Tables

Watt and Merrill

Wealth of India

Miller (1958)

Gohl (1981)

ZERO-MOISTURE SUBSET

5. AGROFORESTRY

Ecology Subset

Germination Subset

Cultural Subset

Nutrition Subset

Utilization Subset

Yield Subset

Wood Characterization Subset

Pest Subset

INTERCROPPING

6. PEST (fungi and insects only)

7. ETHNOMED

Colloquial Name Subset

Pesticide Subset

Pharmacologically Proven Subset

Cancer Subset

Malaria Subset

Geography Subset

Ailment Subset

Source

One of our most productive activities was mailing over 1,000 questionnaires worldwide to scientists and extension people, intentionally emphasizing developing countries. Within 2 years, over 500

people had responded, sending published and unpublished ecosystematic data (annual rainfall, annual temperature, soil type, soil pH, elevation, etc.)

on economic plants and some weeds and nitrogenfixing species. These data, related to about 1,000

species, now are incorporated in the Ecosystematic

File (fig. 1) and are tabulated in The Quest for

Tolerant Germplasm (4).

A success story addressing the multimillion-dollar problem of iron-efficient sorghum germ plasm

illustrates the potential value of the ecosystematic

file in seeking germ plasm for extreme environments (6). Scientists from the Plant Stress Laboratory were incredulous at the high soil pH reported

for Sorghum bicolor in the file. Most sorghums are

chlorotic and nonproductive on alkaline soils. The

scientists asked for more information on the high

pH sorghum. Since each species in the file is recorded with the name and address of the reporting

scientist(s), the computer was able to provide a

mailing list of 14 correspondents who reported

sorghum at pH 7.5 or higher. Letters were sent to

10 of the correspondents. Four responded with

seed, two lots of which were iron-efficient sorghum

which grows and produces without chlorosis on alkaline soils in the Western United States. Now we

are cooperating with the USDA Plant Physiology

Institute in a search for soybeans tolerant to

aluminum toxicity.
The USDA Economy Botany Laboratory’s Data Base on Minor Economic P/ant Species ● 197

Figure 1 .—Sample Page From “The Quest For Tolerant Germplasm”

Scsam um radialum Wild scsn]nc

.—

‘1’111 1’,1[ 4.3-5.0 25-4 0 25-27 AF 64

Scstbania birpino~a Canicha Wm Tvm A,S 4.3-7.5 G-J3 16-29 111 12,24

.$esbania exalt ala Ilcinp se bania Wm Tdm P,A,l I 4.5-7.3 7-25 13-27 NA 12

Sctaria ilalica Ilulian nil Ilct Clnw Tvw A,G 5.0-8.3 3-4 2 6-27 CJ 18

Sctaria sphacelata Golden L:nolhy (Mm Tvm P,G 4.3-7.1 7-3 3 11-27 AF 18,36,54

Sicana oriorifera CilSClt)i311i na Sdm Tvm P,V 5.0-8.0 7-2 8 21-25 SA

Simarouba glauca Aceituna Sm

Sim mond$ia Chirrensis

‘i’dm P,s:r 5.3-8.0 11-2 5 21-2 7 M A

Jojoba Wxt ‘rd P,S,T 7.3-8.2 2-11 16-26 MA 56,*1OO

S8napi3 alba White rnuslurd

Smilax ari~tolochiifolia

Blnw Trl A,l[ 4.5-8.0 4-1 8 5-24 ME 24

Sarsaparllla Wm Sm P,S,L 17 18-2 3 M A

Solarium aethiopicum Mock tolnato Cm Tm P,S (3.2-6.2 9-4 0 9-25 AF 24

So fanum auiculare Australian nifjhtshrrde Crnw Wdm P,S,T 5.5-8.2 7-1 3 12-17 AU 46,48,92

Solarium ferox Ram-bcgurr Cm Tw P,}l 4.5-5.0 7-42 83-27 111,11 24

Solarium gilo Gilo Tm P,S 4.3-4.8 27-3 3 26-27 AF 24

Solauum hyporhodium Cocona Sdw P,s 6.5-7.3 7-3 1 21-23 SA

Solarium incanum Sodom nj)plc Sdm 5.5-7.8 8-1 7 19-2 3 AF,III 24

Solarium indicurn Indian rrlghlshade Sdm ‘rxw 4.3-7. 8 2-4 2 1’3-27 11[,11 24

Solanurn khasianum Solarium khasianum C w Wm 11 5.0-6.0 9-1 3 13-1 5 1{1 24

Solanurn Iociniatu m Kangaroo apple Cmw W d P/A,S,T 5.6-8.2 7-11 12-15 AU 48,92

Solanu m mucrocarpon Native eggplant Ww Tdm 11,s 4,3-5.2 13-37 18-27 AII” 36

Tolatturn melongcna Eggplant Csw ‘rxw P/A,ll 4.3-8.7 2-4 2 7-2 8 CJ,III 24,36,48

So[,lr[u m m uricntu m Melon-pear Sdm Tri 1’,s 5.7-7.3 7-1 5 18-25 SA 24

Solanu m niqum Dlack nightsl]ade Bw T x w A,l{ 4.3-8.4 2-4 2 5-2 7 AF,ES 24,36,48

Solun utn q UI loense Lulo Cmw T d PJI, S 5.8-8.0 7-3 1 11-25 SA 24

Solarl um (oruum Tcrongtill Cm ‘1’vw 4.3-8. 7 7-4 2 9-2 9 N’IA }{ I 24

Solan u m lu beru$u m

——

I’olirto Bmw TVW A,l{ 4.2-8.3 3-4 6 4-2 7 SA,hl A,ES 24,3i3,48–

Solcrrostemon rofundifolius I lausa potato Sm ‘I’d P,ll 5.0-5.0 13-17 23-26 Ak’ f84

Sorgliastrum avenaccurn Indian gritss Wm ‘I’d P,G 5.6-7.1 11-17 12-26 NA

Sorghum X almurn Almum ~orghum Csw Tvd P,G 5.0-8.3 3-25 9-26 SA 40

Sorghum bicolor Sorghum Csw ‘1’tw A,G 4.3-8.7 4-4 1 8-2 7 CJ,II1,ME 2 0

t For nuthorilics on mosl of lhcsr spcci,s, scc I)ukr rrnd Tcrrcll (1974).

~ Following }Ioldridgr (1!347); T-Tropic~l, S-Sul>tropical, W-Wnrnl Trmprra~c, C-Cool Tcmpcrnte, i)-llorcnl; x-Desert, t-Thrsrn, s-Steppe,

v- Vrry Dry, d-Dry, m-hloist, W- WC 1 and r-Rat ~1.

~ A-Annual, Il=i)icnnial, P-i’crennial, I’/A-Perclnial lmatcd as an annual, II=llcrb, G-Grass, L-Liana (woody vine), S-Shrub, T-Tree, V1 lcrbaccous vine. ●

1

Avcrflgc of monthly means wilh valuci below 00(’ trcalcd rrs O.

Ccnlcr of divcrsily, trascrl Iargcly on Zcvcn nnd 7,hukovsky (1975) and Plant Taxonomy files. The first symbol cilcd is possibly a center of

origin. , CJ=China-Japan, 1 l-lndocllilla-l llrloncs’:1, AU-Auslralia, 1+1-l linduslani, CI~-Conlrrrl Asia, NE-Near East, ME-Mcriilcrrnncan, AFA[rlcn, ES-Eurosibcrinn, SA-South Amcricn, hl A-hlidrllc America, NA-Norlh Amrricn. For space conscrvnlion, nrr Inorc lhnn lhrce ccnlcrs

nrc listed.

tl’ Diploid chromosome numbers based Inrgcly on i rlorov (1969), Zcvrn and Zhukovsky (1975), and unpublished compilation by Mac}ierrry Sllff.

Only three counls nrc Iislcd IIrrY, bul mnl)y more mny hnvc been rcporlcd.

SOURCE: Duke, J. A., “The Quest For Tolerant Germplasm,” ch. 1, pp. 1-61, ASA Special Symposium 32 “Crop Tolerance to Suboptimal Land Conditions” (Madtson,

Wis.: American Society of Agronomy, 1978).

Yield File

In addition to data from the questionnaires, data

from publications of experiment stations have been

entered into the Yield File. We regret that we cannot keep up with this literature; the entries probably

account for less than 1 percent of the yield data

published annually by experiment stations, By increasing the data included in this file, which is impossible at our current level of fundin,g people

could be told the yield of exotic crops (with various

cultural inputs) grown in areas ecologically similar

to theirs. The Yield File is clean and useful now,

though off-line. With major backing, it could help

strategists predict yields of new crops in particular

areas.

For a brief period, funding was available to promote one subset of the file, the Phytomass File (fig.

2). (Phytomass is defined as aboveground dry-matter yields of plants.) Department of Energy (DOE]

support for that file has been discontinued but

some institutions such as DOE or Oak Ridge may

have similar files. Data from the Phytomass File

support our early contention that C4 grasses are

roughly twice as productive as C3 grasses, which

are in turn roughly twice as productive as legumes.

Availability of this kind of information could save
198 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Wo&shop Proceedings

Figure 2.–Sample Page From Phytomass File

. .

DA~ xm

Under Source, M - Berbase Abstract

SOURCE: Duke, J. A. “The Gene Revolution," paper No. l, pp. 89-150,C)ffice of Technology Assessment, Background papers for Innovative Biological

Technologies For Lesser Develped Countries (Washington, D.C; U.S. Government Printing Office, 1981)
The USDA Economy Botany Laboratory’s Data Base on Minor Economic Plant Species • 199

countless hours and dollars in screening projects

where maximum biomass production is a priority.

Climate File

The easiest file acquired was the Climate File. It

is the computer tape to Wernstedt’s World Climatic

Data (1972) and was purchased for less than $200.

USDA colleagues have converted the temperature

data from Fahrenheit to centigrade, and the rainfall and elevation to metric units. The monthly

means for these 18,000 stations now are compatible with hundreds of climatic figures gathered

through questionnaires and publications. Monthly

precipitation and temperature data for about 20,000

stations now are integrated into the Climate File.

A species’ ecological amplitude can be determined

by using this file in conjunction with ecological

data for geographical areas from which the species

is reported. For example, if one wanted to know

the ecological amplitudes of a species that is not

in the Ecosystematic File, one could consult herbaria and publications for locales where the plant

grows, choose those that occur in the Climatic File

and, using the computer, obtain climatic highs,

lows, and means of these areas. Further, one could

pick potential germ plasm sources that are most

similar ecologically to the germ plasm recipient.

This important germ plasm matching capability applies not only to minor, underused economic plants

but to cultivars and varieties of the big dozen. A

sample page from an early version of an economic

amplitude paper appears in figure 3. This file has

been used in the USDA Plant Physiology Institute

at Beltsville by colleagues who are interested in the

tropicality of members of the Malvaceae. They are

studying the distribution of malvalic acid, an acid

possibly involved in responses to temperature

stress in cold- and heat-tolerant mallows.

In a seminar at Beltsville on March 17, 1982, Dr.

G. L. Stebbins introduced a list of cold-tolerant to

heat-tolerant legumes, speculating that the greater

the DNA volume, the greater the cold tolerance.

Without consulting the Handbook of Legumes of

World Economic Importance (5), wherein the

ecosystematic amplitudes of species are published,

I predicted that the legumes’ mean annual temperatures would line up inversely with Stebbins’ DNA

prediction. The lineup was almost perfect, as depicted:

DNA Mea n

volume (from temperature 0C (from

Stebbins seminar) Handbook of Legumes)

Vicia faba –—–––——– 26.7 12.1

Pisum sativum ., ., . . . . . 9.8 12.9

Phaseolus vulgaris . . . . . . . 3.7 19.3

Glycine max . . . . . . . . . . . . 2.2 18.2

Lablab purpureus. . . . . . 0.7 21.9

The Climatic File can be used to address problems in the global carbon cycle. Tropical forests

play an important role in the global carbon cycle

because they store 46 percent of the world’s terrestrial carbon pool (1). Brown and Lugo presented

data for each of several Holdridge Life Zones, projecting total forest biomass, soil carbon content, net

carbon content, net primary production, wood production, and leaf litter production. The EBL has formulae for converting its 20,000 climatic data sites

into Holdridge Life Zones and, using a computer,

Figure 3.—Sample Page Showing Ecosystematic Data For Malvaceae

G!Ultl A AS IATIU L. 6.6 20.2 4:.9 (4) 14.7 II .4 27.4 (4) 6.8 ;.2 7 .’

=1-.i LA ~LIA A

(:\

hch. 9 0 14 K z- 8 (6) ~9 A 6 26 6 (6 4 5 s- 1 (4

TRllhFFllA W?&IOU J&. 6:7 20:L 4;:9 (2# 18:7 24:6 27:4 (11; 5:0 0:: ;:1 (9;

TF.l WHITA ~1’WA bJ 6.7 11.1 42.9 1s.7 23.4 27. 4 (6) S.o 0.3 7.1 (4

FMILY kwvmw Z.b 14.1 42.9 (S13) 7.0 22.6 29.9 (312) 4.3 6.3 8.7 (211;

UIXOUS ~L&’ti (L. ) Wench. 2.6 14.3 J1 .0 (107) 11.1 24.4 Ins (}~) 4.J :.; :.7 (4;)

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(4/) 4 . .u 0.6 Li z 16;

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IX&SYPIU4 lMRMD2JSE L.

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4.9 13.5 40.3 (2S) t.4 22.6 27.6

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(25) 4.S 6.S 8.4 (19:

KKsYPILK! KWJACUN L. S.1 11.9 4:,9 [16) 3.2.s 20.7 :7. $

CUiTYPIU4 HIW2.MM L. 2.9 11.3 27.8

5.5 6.9 B.4 (13’

(M) 7.O ~@. ? ~~ .*

~bCA\~= L

6.6 6.4 ;3: t

SINMJll FFA L:

s - 14 9

6:: 17:9 4Z:9

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~

6:1 t:: (18,

A L. . . . . 5 (Ii) N

 -

., 2 . . .> ,, . . . (.1s.

FAMILY =~ 4.8 ]6.9 42.9 (136) 1$.0 2s.3 28. S

K7B4X CEIM L,

rclti \L. ) tact-u-t. 4 .&

Rlo ~n.lrl. 13.5 . ., . (l (/ 7- 7 1 ->. .0. 4 ( 7 ) 4.3 S.6 6.6 1

FAMILY Sl_EWXL~ 4.8 16.8 42.9 (141) IS .0 25.4 29.9 (140) 4.3 6.2 8.7 (66)

CTIA N2D41NATA (Beam. ) Wwtt C Emil. 6.4 19. B 40. 3 (12) 21. S 2S.2 26.6 (12) 4.5 5.5 1.0 (7,

1S.6 22.0 ~.8 6) 25.3 2S.4 26. 6 (6) 4.s 4.5 ~.> (4)

. . . 3 iLi7. . 5 2“0.5 (> I 4.8 6.4 5.0 (31

TtiSIBW4A OfXO L. 4.8 16.3 42.9 (ltij 11. o 2s.3 2! .s (]08j 4. 3 6.4 6.7 (i3j

SOURCE: Duke, J. A., “Ecosystematlc Data on Economic Plants,” (Wart. J. crude Res. 17, No. 3-4, 1979, pp. 91-110,
200 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

can generate Holdridge Life Zone maps for countries not now mapped in the Holdridge system. We

then could project standing biomass, total carbon,

and annual productivity of the zonal forests,

based on Brown and Lugo’s numbers or refinements thereof, and give real or projected yield

figures for high-biomass grasses, energy-tree plantations, or conventional crops for these Holdridge

Life Zones. This could provide some guidelines for

choosing the best crop-agroforestry combinations

for agricultural development in Third World

countries.

We believe that the climate of some remote area

can be deduced by checking the ecological amplitudes of dozens of perennials growing there better

than by measuring the rainfall and temperature for

1 year. The fig, scuppernong, and pecan at my

Howard County farm are near their northern productive limits; the ginseng, rhubarb, and sugar

maple near their southern productive limits. Based

on these species, the mean temperature at my farm

can be predicted to be between 110 and 130 C.

Dr. Peter Raven, director of the Missouri Botanical Gardens, asked us at what locations in the

world the climate was most similar to that of the

Missouri Botanical Garden. If asked simply for annual temperature and annual precipitation, the

computer would indicate many places that do not

have the temperature extremes of St. Louis’ continental climate. Introductions from maritime climates with identical mean temperatures might be

killed by the summer heat and/or winter cold of St.

Louis. A continentality variable, which will differentiate among climates with similar mean annual temperatures but different vegetational potential, has been added to the Climate File.

In October 1982, EBL was asked to name locales

in Latin American where date palm would grow.

As a test case, Dr. Atchley at USDA and I each devoted no more than 4 hours to this query (app. I

and II). The difference in conclusions reached is

due to Dr. Atchley’s assuming rainfed conditions

and basing his projection on actual reports for date

palm, and my assuming an irrigated situation because artifical or subsurface irrigation is implicit

in most of the good date-growing areas I cite. The

computer provided lists of possible sites for date

palm under both irrigated and rainfed conditions,

and eliminated hours of searching through 20,000

climatic data points.

The narcotic-replacement program led us to the

coqueros, the cocaine-leaf chewers of the Andes.

The coca leaves chewed by these Andean Indians

are high in calcium and iron, more so than any

plant food in the Food Composition Table for Latin

America (fig. 4a). Calcium and iron, as well as certain vitamins and proteins, often are deficient in

diets of the farmers we were trying to divert from

cultivating the coca (“cocaine”) bush. The problem,

therefore, was one of both nutrition and crop substitution. What commercial food crops could the

farmer grow as substitutes for coca? To answer this,

we needed to know their climate. However, they

might be 100 miles and 10 mountain ranges away

from the nearest climatic recording station (that

ceased recording 10 years ago). This quandary

spawned our Ecological Amplitudes of Weeds program. We added weeds to our questionnaires to

help predict climate in remote areas (fig. 5).

Another use of the Ecological Amplitudes of Weeds

program is in mapping the potential for an alien

weed to spread in the United States. Determining

ecological amplitudes of a weed by consulting its

distribution and extracting climatic data from the

Climate File, we can determine where in the U.S.

the climate is most closely and least closely

matched.

Nutrition File

For the Nutrition File, we used at least one credible entry for each plant species in Food Composition Tables for East Asia, Africa, and Latin America, from Watt and Merrill’s Composition of Foods

(Agriculture Handbook No. 8) and from The Wealth

of India (C. S. I. R., 1948-76), computerizing the proximate analyses of hundreds of botanical. I scored

the plants’ nutritive contents (elements, vitamins,

calorie and fiber content) as extremely low (E), low

(L), high (H), or very high (V), relative to USDA’s

recommended dietary allowance (RDA) (fig. 4b).

Unfortunately, I had overlooked Miller’s Composition of Cereal Grains and Forages (1958), which

consolidated thousands of forage plant analyses, No

sooner had I finished adding this information than

another massive compilation with numerous new

data on forage analyses was published (7). My colleagues at USDA and I are entering these data into

the computer file which we hope will be tabulated

and published by CRC next year.

We devised a computer program to convert our

as-purchased proximate analysis file to a zeromoisture basis (fig. 6). To ensure that only complete

proximate analyses are used, the computer uses

only those columns for which the sum of water,

protein, carbohydrates, fibers, and ash is 100 percent (±1). The computer then multiplies all columns except water by 100 ÷ (100=X), where x
The USDA Economy Botany Laboratory’s Data Base on Minor Economic Plant Species . 201

Figure 4A.—Nutritional Composition of Coca

Nutritional comparison per 100 g of Coca Leaves with other Latin American Plant Foods

FOOD ITEM 7 in Cal H2O Prot. Fat Carb. Fiber Ash Ca p Fe Vit A

l Thia Ri b Nia Vit C

sample g g g g g g mg mg mg IU mg mg mg mg

.—— —

San Francisco coca (1) 305 6.5 16.9 5.0 46.2 14.4 9.0 1540 911 45.8 Ilxm 0.35 1.91 1.29 1.4

Bolivia coca (3) –? 8.8 — 1.6 42.4 8.0 53 — — — — — — — —

Peru coca ( 3 ) — 103 18.7 — — 17.5 4.6 2038 363 7.9 9,000 0.81 1.55 6.17 —

- .

COCA AVERAGE {7) — 8.5 18.8 33 44.3 13.3 6.3 1789 63 7 26. 8 10,000 0.58 1.73 3.7 1.4

PLANT FOOD

AVERAGE (50) 279 40.0 11,4 9.9 37.1 3.2 2.0 99 270 3.6 135 0.38 0.18 2.2 13.0

Nuts & Seeds (10) 521 9.9 16.8 36.0 28.2 3.6 3.1 273 522 4.3 17 0.78 0.28 5.2 2.1

Pulses ( 10) 354 11.3 25.4 5.0 55.1 5.5 33 102 398 7.1 20 0.58 0.24 2.25 1.9

Cereal s ( 10) 352 11.5 11.7 3.7 71.0 4.0 2.1 74 346 4.8 13 0.41 0.25 2.7 0.8

Vegetables ( 10) 74 87.3 1.8 0.4 16.9 1.5 0.9 26 52 12 595 0.09 0.05 1.0 31.0

Fruits ( 10) 93 79.6 12 4.5 14.1 1.4 0.7 20 33 0.8 35 0.05 0.06 0.08 29.0

SOURCE” Duke, J. A., Aulik, D., and Plowman, T. “Nutritional Value of Coca,” Botanical Museum Leaflets, vol. 24, No. 6, (Boston, Mass.: Harvard University, 1975), pp. 113-119.

equals water percentage. The completely new and

unique table has hundreds of species compared on

a zero-moisture basis. The Nutrition File (as purchased or zero-moisture) can be linked through a

species’ scientific name to the Yield File to convert

yields to protein per hectare instead of grain per

hectare, and to the Ecosystematic File to show

which will yield the most leaf protein per hectare

under any specified combination of annual temperature, annual precipitation, soil pH, etc.

Before the National Cancer Institute discontinued

its support for the EBL data base, we started a file

on biologically active compounds to parallel the

Nutrition File. It indicated the toxic compounds

and their LD50’s for plant genera (fig. 7). We regret

that other quantitative data were omitted, Dr.

Farnsworth’s comprehensive NAPRALERT program dwarfs our attempt at computerizing biologically active compounds in plants. Since he also

uses plants’ scientific names, his pharmacological

data could be sorted against any one or all of our

data files, using the scientific names to link the two

data bases.

Ethnomed File

It is ironic that the Ethnomed File (fig. 8), with

which I worked most closely for nearly 5 years, is

now the lowest priority file. The file was built to

encourage Third World countries to supply medicinal and poisonous plants for a collaborative screening program with the U.S. National Cancer Institute. With 88,000 entries, the Ethnomed File is

probably the largest extant computerized data base

for folk cancer remedies and is quite good for general folk remedies. Pesticidal activities, of greater

current interest to USDA, also are included (see fig.

9 for insecticide subset sample). This file can interact with any other file through the same scientific name.

Ethnomed is not dead; it lives on as a much consulted printout. For example, we have been asked

to help an NIH contractor prepare a prioritized list

of Nigerian species for antimalarial screening (fig.

8). The malaria entries marked with an asterisk contain compounds with proven antimalarial activity.

The species marked with a double asterisk correct

or alleviate malaria. Unfortunately, the common

name file is incomplete. It would be useful to many

agencies, since many plants are recorded by common rather than scientific name. Interlocking scientific names with the name of a country from the

Ecosystematic File should show not only which antimalarial species occur in that country but should

give the names and addresses of the people who

reported them, Using the ecosystematic amplitudes

of the target species, the computer could indicate

the country’s climatic stations within the ecological

ranges of the target species. For example, the computer could name many antimalarial species occurring in Nigeria and list villages suitable as staging

areas to search for the species.

24 - 503 0 - 83 - 14
202 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Figure 4B.—Sample Page From Vegetarian Vitachart

wild grape (q

wild lettue (1)

wild -O(f)

wild plus (f )

uild rice

Uilloulcaf bxmxl

wine palm

tArlged yam

ti?&cd yam wintersquash (~

tiwrsquash (1)

“wintcrsquash (fl)

wlfberry (d, ~

KMb’erry (1)

d oil nut wmly -z~tita

uonrueed (1)

m

+an (r Y==7tka

yxmbesn (r)

*OW F= “04 ~hylya u)

ywtla (r)

yebbmt (s)

ye:;: ho lua (f) ain (f)

yellow rmAti (nut)

Vith tiliifolia

Lactuca taraxacifolia

I~ia gabonens~

Bcqw.emiodendmn

lrbsgalkmrunus

Ziz& aquatia

Lucu7u salicifolia

Hauritia vinifera

Dioscorea data

Dioscorca alata

(kurbita rnaxhm

Cucurbita mxixa

tkurbiti maxk

Lyciua Chilunsls

LyciKs chinensis

Ridmdmdmn heudelotfl Arc*As*t22hylos tmcntcsa

Chcnopodlm aAmosioides

Diosco-pa S po

P*M-zus-angulatus

Sphenostylis Swmcarp

hch)TAizui-i?p7

Vifp GngulculAta

Vigna Unguiculata

xanthoscSM Sp.

Xanthosma Spo

Cordeauda edulis

Spondias CIx’’fll

SpendiaS axTMn

Sptmdias rldlin

yelloutaper candletree btiers ● dcata

LLHH LL LL L E H

HLH L L

LLL H L L v

LLH L

LHHHH;&Lh;E~Eg

LLHL HL HLH

HLV H ::

LLL L itHLLE~gl

LLHL L L

LLL L L L .H t t E : ; fl

HLH L LHHLHELHE

HEL H LLLLLELLH

LHV V HHHHVLHVV

HLHH LLHLHLLVH

HHHL EV HE EEE

LU LE L H V

HLHH :; LHH

LLL L LL H:: LEH

ELHL LL LL LEH

L L L

LLLL L; ;’ L LEH

LLH L LLLLLELLjl

HLHH LHHLHEHHH

HLHH H L VH

LLH L H

L H% H k k

ELLE LL EL

LLHH L L :L:

LLLH L L :: L L H

L L V LH LL HLH

yellow vdn (1] Pseudcrantkua reticulate LL LL L H V

Pm Cumnmopsis eddh H;: H

w= (m Yxu elcphamipes LLLL L: LL H E V

W=$ (A) Ywx elcphantipes HLHL LL LL HEH

1d . &y, f . fit, fl - fi-rt ~

 -

-c 1 - ldt 9- amturu, r - mot, s . s~, Sh . s-t (or M).

SOURCE: Duke, J. A., “Vegetarian Vitachart, Quart. J. CrrJde Drug Res 15, 1977, pp. 45-46.

We receive daily inquiries from all over the world

asking what herbs are used for what ailments. One

Senator asked us for opinions on various quack herbal medicines. Another Senator has shown an interest in the so-called “petroleum nut” Pittosporum

resiniferum (fig. 10), an energy plant endemic to the

Philippines.

Thanks to three professors in the Philippines, we

now have seed and a fairly good idea of the ecosystematic amplitudes of the Pittosporum. One professor indicated where Pittosporum resiniferum

was growing prior to widespread relocations in the

Philippines for potential energy studies. This information was paired with climate stations in the Climate File to yield ecosystematic amplitudes. Ranging from Tropical Dry to Moist through Subtropical

Forest Life Zones, the petroleum nut grows where

annual precipitation ranges from 15 to over 50 dm

(mean = 27 din), annual temperature from 18-28°

C (mean = 26° C). Of 17 cases where both

temperature and rainfall data were available to us,

13 were found in the Tropical Moist Forest Life

Zone, three in the Tropical Dry Zone, and one in

the Subtropical Rain Forest Life Zone. A similar approach could be used to determine the ecological

amplitudes of a medicinal plant, weed, or promising new economic species from the thousands of

species not among the thousands already in our

computer.

P~pe8

We have developed the following three data base

prototypes which could be expanded readily if priorities dictated.

Agroforestry File: This program was developed

for several species being considered for agroforestry. Different subfiles contain information on eco-
The USDA Economy Botany Laboratory’s Data Base on Minor Economic Plant Species . 203

Figure 5.—Ecological Amplitudes of 100 Perennial Weeds

Ecological amplitudes of 100 perennial weeds*

ACACIA FARXESLIN4

.4CER SACCH4RU31

.4CORUS CALWUS

.AG4\T LECHkGUILL4

AGROPYROS REPi3S

AGROSTIS STOIJMIFERA

ALOPECURUS PR4TESS1S

.~J”sI-s VAGISALIS

Afr,QpHI ~ ~~~IA

/L\_DRLW’OGON GiXARDI I

ARCTIUYI L4PPA

ARRKENATHERM! EL4TIUS

ARTE!.IISLA ABSI>THILN

ARUSDO LxNu

ATRIPLEX CANESCENS

AXOWPUS CC$PRESSUS

BO13+ERIA NI\’E4

BRACHIARIA MUTICA

BROIUS INW1lS

C4LTH4 PALUSTRIS

C4RY.LI ILLIiWENSIS

CASSIA AURICUL4TA

C2V5TANE4 D13WATA

CHEWPODILN A~DROSIOIDES

CHLORIS GAY.4NA

CICHORILN IIN~’BUS

CLITORLA TERNATEA

COICCOLOBA LR’IFER4

C0ROSILL4 \’ARL4

COR}’LUS CORWTA

C)’xw C4.RWW* -uLus

CWWIXIN D.K13’LON

C}’ PERUS ROTLNDUS

DNTYLIS GL01ER4TA

DICH%’YTHIUM M!!ULATLBl

DIcHo\!R4 REPEM

DIGITARIA DECUllBEM

DIOSP}’ROS VIRGINIAN!

ECHI,WCI-MA CRUSG4LLI

ELELXHARIS DULCIS

EQUISETIJM ARVIXSE

ERAGROSTIS CUFW’ULA

FAGUS G’lkVDIFOLIA

FF5n!r.\ .l~USO!\:Jc:!

FOLNICUIXM \ULGARE

FR4G4RIA VIRGIfiIAM

G.E.NISTA TI~ORIA

G~WIfWIA IAJTEA

G~}”~~+~~fl. GL’~R~

HELIAN17+US TUBEROSUS

HORDELN BULFWW1

tn”PARRIW!IA RUFA

INUL4 HELENILN

JUGMNS NIGRA

JUNIPERUS CO! NUSIS

LESPEDEZA STRLATA

LESQUERELL4 GORKNI1

HUIS.4CHE

SUCAR FWLE

Sh’EETFLAG

LECHEGUI LL4

QUACKGRASS

CREEPING BL\TGRASS

MEADO\< FOXTAIL

AL>’CE CLO\IZR

EUROPEW BISWHGRMS

BIG BLUEST131

GRMT BURDKK

TALL OATGR%SS

.4BSIkTH Ni3RJlW~D

GIAN REED

FOURh’ISG SALTBUSH

TROPICAL C4RPETGWSS

~LIIE

PARAGRASS

SMXYl?+ BROhlE

MAWN4R1GOLD

PEGLV A\l~~l

AMERICAN CHEs’11,’ur

NfEXICAATE4

RHODESGRASS

CHICORY

BLUE PEA

SEAGR4PE

TR41LING CROWTTCH

BEAKED HUEL

CARIx30!i

BER~W’D.4GRW

PURPLE WTSEDGE

ORCH4RDGR4SS

DIA2 BLUEST131

DICHOMIR4

P.4XOLAGRWS

PEW L~fi13\

BARNYARDGRASS

WTEFWJT

FIELD HORSETAIL

WEEPING lJ3\%GRASS

WZRI(AY BEECH

T.4LL FLSCLIE

CCMION F13XEL

VIRGINIA Strawberry

DYERS GREINWD

YELIJlh’ GENTIAN

c~~!~x LICo~~cE

JERLISAIJ31 ART ICWKE

BULBOUS R4RL~’

JAR4GW GRASS

ELE.GWPAYE

BL4CK h:4L\~

COMKIN’ ~’IPER

JAPAM5E LESPEDEZrl

mm~ BLUIDERPOD

h’d Tm

Cmw Sm

Cm Tvw

h’t Ttv

%-m St

Bm \(m

B~ h’t

Sm Tdii

Cmh’

Bm Csm

Cmh h’tm

Bmh’ h’tm

Cmw Sd

Ch’ Tdw

}(t

Sm Tmw

Wm Tvw

Sdh’ ?VW

Bmw Ktd

Grrh’ Wm

htm Sm

Sdm Tvw

Csm hin

CK Tdw

Cs Tvw

Bm Tvm

Sdm Tvw

Sdm Tvm

CmK h“dm

Bm Cw

CmK Ntrn

Csk TXTJ

Bm Tw

Bmh %

Sdm Txm

Iidm Stm

.% Tdw

h’dh’ .$m

Bmw T\’w

S&I Td

hi Tw

cSh’ Td

Ch” Sm

:., --,, c.

h’ i;m

Brm+’ Sd.m

Cm+’ h’d

Cmw Mm

‘-“, , lit

Crrrw Tm

Cs Sd

Sdh’ Tdw

Cnm’ h’dm

Cmh” Sm

Brmi Td

\(dm Sm

lit

4.2-8.0

4.5- 7.3

5.5-7.5

7.0- 7.7

4.2-8.3

4.5-8.3

4.5-7.8

4.2- 4.8

4.5-6.2

6.3- 7.5

4.5- 7.8

4.5- 8.3

6.3- 8.2

5.5-8.5

7.3- 8.0

5.8

4.5- 7.3

4.3- 7.9

5.3- 8.2

4.8- 7,5

5.8-8.3

4.3- 7.3

S. 8-7.3

5.5-8.3

4.3- 8.3

4.5- 8.5

5.8-8.0

5.8-8.0

5.8- 6.8

5.8- 7.5

5.0-8.3

4.3- 8.5

4.5-8.5

4.5- 8.3

5.7-7.5

5.0-8.3

4 .:-7.8

5.8-8.0

5,0-8.3

5.5-5.7

4,5-7.5

4.3- 8,3

4.5- 6.8

9.2 .5. :

5.7-8.3

5.3- 7.5

4.5-7. 5

5.8- 6.8 .06. 2. a-o.-

4.5- 8.5

5.8-8.2

4.5-6.2

4.5-7. 5

5.8-8. 3

4.5- 7. 5

5.0-8. 8

7.3- 7.8

6-40

5-15

5-4?

~-6

3- ‘1 j

5-17

3- 17’

10-42

5-11

5-11

3-15

5-16

3-1 j

3-40

5-5

11-40

: -40

8-5:

3-17

4-14

5-15 7-4?

5-11

3-42

3-40

3-40

7-42

11-25

6-40

4-9

5-12

3-42 j.~~

3-2 1

2 - 8

3-1 5

g- 26

7-17

3-2 3

8-2 3

5-25

3-15

2-15

;- :A

3-26

4-17

7-1 1

7-11

:-:

:-;8

8-40

5-13

3-13

4-11

5-17

3-9

o-II

o-s

5-12

~ -5

0-9

0-6

0-6

9-12

2-6

0-11

0-6

0-6

0-6

0-11

--

S-12

1-12

s-l?

o-s

O-6

0-7

S-12

5-5

0-12

0-12

(-J-12

S-12

5-12

2-11

o-s

O-T

0-12

0-12

0-9

0-6

0-9

4-12

1-9

0-12

5-10

0-9

()-g

j- y

0-12

1 - 9

1-6

1 - 6

7

~;i~ .

0-5

4-12

1-6

0-6

0-6

3-9

--

* For explanation see text.

SOURCE: Duke, J. A., “Perennial Weeds as indicators of Annual Climatic Parameters,” Agricu/tura/ A.feteoro/ogy, 16:291-294,

(Amsterdam: Elsevier Scientific Publishing Co., 1976).
204 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

0

0

0

Z-u u - z

0

k

. o.

0

Z-u v-z o

0

0

0

0

.

.

n

u

v

aJ

0

dwN

m

.

al

.

w

0

0

G0

0

0

0

o

0
The USDA Economy Botany Laboratory’s Data Base on Minor Economic P/ant Species . 205

Chcmml

Qurnaldmr

Qurnazoline

Quuuc acid

Quindi.m

Qumint

Quinolme

Raton

Red squtil

Red thyme oil

Rescin.namrne

Reserpine

Retronwine

RetirroI

Genus a

Figure 7.— Pertinent Pages From Phytotoxin Tables

Toxins: Their Toxicity and Distribution in Plant Genera

TO\ ICIVa”b

orl ral LD, ,, 1,230 mg

skn rbt LD,, , 1,870 mg

sk.n mus TDLo, 4,000 m~f}’1 h’EO

scu mus LDj ~, 10,000 mg

or] rat LD$ ~, 1,000 mg

or] mus LD$ ~, S94 mg

ipr rat LDLo, 114 mg

ipr mus LD, ~, 190 mg

ml wmn TDLo, 20 mg

(4-5 U’ preg) TER

or] rbt LDLo, 800 mg

orl gpg LDLo, 300 mg

USA gpg TDLo, 200 mg preg TER

orl ral LDj ~, 460 mg

Ipr mus LDLo, 64 mg

skn rbt LD, ~, 540 mg

scu rat TDLo, 31 g/61 V’] NEO

orl rat LDj ~, 200 mg

or] rat LDt ~ , 4,700 mg

or] mus LD, ~ , 1,420 mg

or] hmn TDLo, 14 Pp PSY

iins hmn TDLo, 357 Pg PSY

unk rat TDLo, 1.500 Bg

(9- 10 D preg) TER

IWI rat LD, *, 1,311 rrsg

ivn mus LD ,,, 634 mg

Family

Rubiaaae

Laura-e

or] rat TDLo, 5S mg

Clm”umb Asteraceae

O“ssusb Vjtarxae

a“sfus Cistaceae

Plant gencrs

Colipca

Dtihroa?

A conitum, Angelica, A rc!ostaph>los. Cinchona,

Daucus, Euca!>”prus, Illicrum, Linunr. MOIUL

Medlcago, ,Vicorianc, Plsrocia, Prunus, Rosa,

Terminalio, Vaccinium

Cinchona, Cou Iorcc. Enanti, RcM~w, Srr},chno$

Cinchono, Corrrus. Coutorti. Enantic, Ladenbe~,

A“crolemma. Renrrjia. Stnchnos

Cilms

Glin”cidirr

Scilla

Thyrnus

Rauw’olfw, Torr&zia

A Istonia, A spldosperma. Bleektrio, Excaroria,

Ochro~ia. RcuW%l.fu. Tondu:ia, V’allesw. Vinca,

Voawrrga

Usually combin& A msinckio, Brach.sglorris,

Cwraloria, k cAu8m. L n)ilif. Lrrcll tites.

Heliorropiurn, ?’i:asltcs, Stnecio, Trichodesrna,

Tusrilago

M’idesprcad?

TABLE 2 (con?inucd)

Higher Plant Genera and Theis Toxins

Toxin

Cinchonidine, cinchonine, quink add, <uiitidine, quinine, s.apc..ln

Awtaldehyde, tmzoic acid, oorneol, c+imc acid, CJFij’~C a&, wvacrol, cassja oil, cineole, cin.namaldeh~+de, cinnarnyl alcohol, citrnellol, coumarin. cuminic alcohol, c-amin.ic aldehyde, cymene,

decanal, eugeno~ eugenol methyl erlaer, formic acid, furfural,

geraniol, hydrocyan.ic acid, isobutyric acid, meugend, isoVdmkiehyde, isovalenc acid, launc acid, Iimonene, Wool, myristic acid,

myristicin, nonJyl alcohol, phellandmm, piperonal, propionic acid,

safrole, Qicylaldehyde, sal.icylic aci~ shikimic acid, tannic acid,

terpineol

Hydrocyanic acid

Hydrocyanic acid

Acetophenone, formic acid

SOURCE: Duke, J. A,, “Phytotoxin Tables,” CRS Critical Rev/ews in Toxicology 5(3): 189-237, 1977,
206 . Plants: The Potent/a/s for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Figure 8.—Sample Ethnomed Printout

Ose

AIA L AR I A

MA L A R J A

MA L A R 1 A

MA L A R 1 A

h~A L A R ] A

MA L A R 1 A

hlA L A R 1 A

?; L L A R 1 A

MA L A R ! A

NA L A R 1 A

MA L A R 1 A

III A L L f{ i A

MA L}, R I A

hlA L“L R I A

hl~ L L R i A

MA L A R : A

h!A L A R 1 A

MALARIA

MA L A R 1 A

t.!A L A R I“A

!,lA L A R 1A

MA L A R 1 A

hiA L AR 1 A

h:A L A R 1 A

hlA L A R I A

MA L A R I A

t.l A L A R : A

MSLA171 A

MA L A R I A

htA L A R 1 A

hlA L A R I A

MA L A R !,A

hlA L A R ;.&

MA t. A R 1;A

MA LA R I*A 4

hlA L A R I A ●

LIA L A R I A ●

hlA L A R I A “

MA L A R I A*

hlA L A R I A ●

MA L A R 1 A ~ MA L A R 1 A ‘

!,1 A L A R i /. *

MA L A R 1 A ●

MA L A R 1 A ●

t,l L L A R I A ●

hlA L A R I A ●

l,i A L A R 1 A “

hlA L A R I A ●

hlA L AR I A ●

MA L fl R 1 A“ *

MA I A H I A* ●

SOURCE: Duke, J. A.,

T RACHE LOS PERMUhl LUC I DUM

TIT I CH1 L I A HAVAIJENSI S

T R I CHOSANTHES CUCUhlER 1 NA

T R I L ISA OOOR& T I SS 1 MA

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T U RNE !?A D I F C d$. L

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VIBURNUM OBOL’ATUM

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v INCETOX ICU:~: AT RATUM

VI SCUhl ALBUM

VITEX NEGUN50

VITEX PEDUNCULARIS

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XANTHIUM SP1)JOSUM

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XANTHIUM ST RUMARIUM

ZANTHOXYLUM PI PER1 TUM

ZING I BER M1OGA

ZI//GIBER OF FICINALE

ZING IBER OF FICINALE

AND IRA IN ERhl IS

BRUCEA JAVANICA

BuPLEURUM CHINEN5E

BUPLEURUM FALCATU!.1

CINCHONA OF FICINALIS

DICHROA FE8RI FUGA

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Eucalyptus SP

LECf/OTIS r/ EPETAEf CLIA

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PC) PULUs ALi3A

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TR!CLISIA GE LLETil

C I NC MONA LEDCE:4!A14:

WION A Qf F i C 1 )Jit !. I S

CMWON

NC

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cH I f/A

HA J T I

E L SE\fi-+ E R E

T K J iq 1 L~A D

! !7 AQ

I z L()

E L SEWH E RE

E L LE ;,’1 t S R :

E L SEkHE R E

ZA 1 RE

MEXICO

h~sx I co

SOURCE.

WO I .10.

STAND LEY. ST EYE RMARK

ST E I NMETZ

KROCHtJAL

WC) I .10

ST ANDLEY

h’o I .10

Wo I .10

ST AND L EY

KROCHMA L

AL T SCHUL

A L T SCHUL

ELI SS

hlA R T I N EZ

W() I .10

EB24: 244

h’o I .10

KROCHMAL

BLISS

BLISS

h’O I . SYRIA

HUNAN

Wo I .10

wO I . SYRIA

WC) I .11

ST E I NhlETz

UPHOF

BLISS

WO I . SYRIA

W() 1.11

BL Is s

BL 1 SS

WONG

EB30: 11 4

MARTINEZ .

NAS

L1

KEYS

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NAS

KEYS

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EB30: 136

v$or4G

AL - RAW I

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w I .10

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hlART I NEZ

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and Waln, K. K., “Madlclnal Plants of the World,” computer Index with more than 85,000 entries, 3 VOIS., 1981.
The USDA Economy Botany Laboratory’s Data Base on Minor Economic Plant Species • 207

u~c

I tt’L L C T I C I DE

J NS EC T I C I DE

I N S E C T I C 10E ( V E T J

INS ECT I C I DE ( VET )

I IJS E C T 1 C I DE*

I N S E C T I C I DE ●

] NS EcT ] c ] DE ,

1 )J S E C T I C 1 DE*

INSECTICIDE*

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INSECTICIDE+*

INSECTICIDE+*

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INSECTIfUGE*

Figure 9.–Sample of insecticide Subset of ETHNOMED

PCANT

ZANIHOXYLUM ARMA7UM

ZAtJIHOXYLUM NITIDUM

DELPHIhJIUhl f3RUNONlANUhI

GARUENIA LUCIOA

ACORUS CALAfitUS

ADHATODA VASICA

Af4t!L’NA CHERIhlOLA

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c~

NC:

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NC

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NC

NC

NC

NC

NC

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NC

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NC

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NC

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NC

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MWTRY

ELSEWHERE

ELSEWHERE

ELSEWHERE

ELSEWHERE

ELSEWHERE

INDIA

LA

ELSEWHERE

ELSEWHERE

NL

INDIA

ELSEWHERE

LA

TRINIDAD

INDIA

ELSEWHERE

ELSEWHERE

LA

ELSEWHERE

ELSEWHERE

ELSEWHERE

ELSEWHERE

ELSEWHERE

ELSEWHERE

ELSEWHERE

ELSEWHERE

CHINA

ELSEWHERE

ELSEWHERE

ELSEWHERE

ELSEWHERE

ELSEWHERE

INDIA

INDIA

ItJDIA

INDJA

INDIA

ELSEWHERE

ELSEWHERE

ELSEWHERE

u s

ELSEWHERE

IF{DIA

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ELSEWHERE

ELSEWHERE

IND!A

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ELSEWHERE

CHINA

ELSEWHERE

ELSEWHERE

Wunct

w~;;

1

UPti&F

UPHOF

Wol,t

WOI.SYRIA

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WO1.1O

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‘h’ol ,3

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ES30: 127

SOURCE: Duke,J, A.and Waln, K.KV “Medicinal Plants of the Worfd;’ computer Index wlthmorathsn 85,000 entrles,3vols. 1981.
208 ● Plants: The Potent/a/s for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Figure 10.—Pittosporum resiniferum

SOURCE: @Peggy Duke,

logical parameters, germination requirements,

nutrition values, cultural requirements, yields,

wood characteristics, use, and plant pathology. A

sample of the Agroforestry File is given in figure

11. Perhaps the greatest impact of the prototype

was to show that almost no data were available on

most nonconventional economic plants. The Agroforestry File is most applicable to Third World

countries.

Pest File: This prototype has only about 2,500 entries. It lists the scientific name of the host plant,

the plant part affected by the disease or the insect,

and the name and type of pest. The scientific name

enables this file to communicate with any other file,

such as the Agroforestry File (fig. 11).

Our ecosystematic file has helped locate herbs important to nematode taxonomy. Nematodes should

be included in any pest prototype, Several years

ago, Russian workers reported a most unusual nematode from a limited area of Russia on Mentha longifolia. Soon afterwards Dr. Morgan Golden found

a nematode similar to Meloidoderita kirjunovae, the

Russian species, on a polygonum at Beltsville. Without Russian specimens or a better description of

M. kirjunovae, it was impossible to make a final

identification of the Beltsville specimen. After testing true Mentha longifolia with this Melodidoderita specimen, Golden found that his nematode did

not attack M. longifolia, the type host for the Russian nematode. With this information and further

morphological study, Golden proved that the

Beltsville specimen represented an undescribed

Meloidoderita species. Without testing with Mentha, the identification and classification of the Meloidoderita would have been much less conclusive.

For years I have campaigned for a program that

would record the ecological amplitudes of pests and

diseases as we have done with economic plants and

weeds, Knowledge of the ecological amplitudes of

crops and their pests could launch a new phase in

biological control of pests’ “biological evasion” (4).

Where the host tolerates more cold than the pests,

planting in the colder area might be advantageous.

For example, in Chowan County, N. C., near the

northern limits of the cotton plant and the boll

weevil, the cotton grows well but the weevil does

not. This lack of crop and pest overlap may be used

to good advantage by the USDA (2).

Intercropping: Because of our involvement with

the Agroforestry project, we had a greater interest

in intercropping than most conventional farming

units in the USDA. My colleague at USDA, Dr.

Atchley, setup a prototype Intercropping file. Now

on tape but not on-line, it lists major and minor crop

combinations, all species in pasture mixes, yield

data, yield differentials, cultural variables, etc.

Using the scientific names to link this and other

files, one could find out which crops have been

tried around the world as intercrops. In densely

populated Third World areas, intercropping clearly promises more quality, quantity, and/or variety

of crops per hectare than monocropping.

Limitations

In intermediate ecotypes, the effects of factors

such as slope, soil porosity, soil type, vegetation

cover, cultural conditions, insolation, prevailing

winds, etc. on plant characteristics may be significant. Few data are available and we have entered

some of these variables for only a few places. This

is a major limitation of our program.
PLNA PLCO AUTHOR

EUCALYPTUS CAMALDULENSIS 453046001 SCti LECHT.

EuCALYPTUS CITn IODORA 453046003 HOOK.

EUCALYPTUS GLOOULUS 453046004 LABILL.

Eucalyptus GLOBULUS 453046004 I.ABILL.

EUCALYPTUS GLOOULUS 453046004 LABILL.

EUCALYPTUS GLOEIULUS 45304GOo4 LABILL.

EUCALYPTUS GLCJOULUS 453046004 LAUILL.

EUCALYPTUS GLOBULUS 453046004 LABILI.

EUCALYPTUS GOMpHOCEPHALA 453046005 OC.

EuCALYPTUS GRAIJDIS 45304600 2

EUCALYPTUS GRANDIS 45304600 2

EUCALYPTUS MARGINATA 4~30460to !jhl.

EUCALYPTUS MARGINATA 45304GO1O Sh!.

EUCALYPTUS MARGINATA 453046LI1O Shl.

EuCALYPTUS hllCRCTHECA 453046006 F.MUELL.

Eucalyptus OCCIDENTALS 45304bO07 ENOL.

EUCALYPTUS SP. 453046GO0

EUCALYPTUS TERETICORNIS 453046006 SM.

Figure 11 .—Agroforestry Pest File

I’IANIS TIIAI Ali[ I’(JI11411 AI fitrt. :[)llllc[~

COMPUTCR12ED BY Tl{[ IGLMIOI.lIC UOTANY LAU(INAIOIIY

ALAN A, ATCHL[Y AfiU C~lC S. hlATtil:

GLEDITSIA TRIACANTHOS

GLIRICIDIA SEPIUhl

GtJELINA ARBOREA

GREVILLEA ROBUSTA

GUAZUMA ULh41FOL1A

HALOXYLON PERSICUM

INGA DOURGON1

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INGA URAGUENSIS

ltJGA jEIIA

LESpEOEZd BICOLOR

LESPEOEZ2 CAPITATA

LESPEOEZ4 CUNEATA

LESPLDEZA CYRTOBOTRYA

LESPEOEZA HIRTA

LESpEDEZA HOMOL08A

LESpEDEz4 PILoSA

LESpEOEZA PROCUtJBENS

LESPE13EZ4 REpENS

LESPCOEZA SP.

LESpEDEZA STIPULACEA

LESPEDEZA STRIATA

LEUCAENA LEUCOCEPHALA

LEUCAENA LEUCOCEPHALA

LKUC&ENA LEUCOCEPHALA

LEUCf.ENA LEUCOCEPHALA

LEUCAENA LEUCOCEPHALA

LEUCAENA LEUCOCEPHALA

LIELIA AZEDARACH

t.l:L”OSA SCABRELLL

L:u,.TIIIGIA CALAE!URA

PI{YLLAIJTHUS EIJULICA

PITtlLCILIODILJf.1 OULCE

PITtlEcELLOOIUf.1 OULCE

pIT}iLcELloO1uLI GuLcE

SOURCE: Econofnlc Botany Laboratory.

28311000 2

283300001 (JACO.) STEUD.

533056001 ROXf3.

12903000t A. CUNN.

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150057002 BUNGE EX BOISS,

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VALID PEST

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1 Ws 114

F HEA 000

F 114

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1 11.1

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TERMITEs I

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●
210 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

We need to get soil taxonomic units from a unified soil classification system for all 20,000 locales

for which we have climatic data. This would require a major cooperative venture. Much more of

the world is mapped in the FAO system than in the

USDA Soil Conservation Service’s Soil Taxonomy.

The Benchmark program is using the USDA rather

than the FAO system for site management.

There is a tendency of some soil scientists to assert that soil is THE determinant in the distribution and yield of economic plants, of some climatologists to believe the climate is the determinant,

and of some plant ecologists to believe the vegetation type is the determinant. I suspect that all plant

distributions are determined by interaction of all

three and other factors as well, Unfortunately, the

computer cannot identify the most important factors affecting a given species. For some species,

vegetation will be the most definitive determinant;

for others, soil; for others, climate. We need a major program to collate the FAO and/or USDA soil

units with the 20,000 climatic data sites, soil pH,

weeds, crops, yields, diseases, insect pests, native

perennials, etc. This should be done for a sufficiently large number of the 20,000 sites to develop ecological (including both climatological and pedological data) amplitudes and means and determine optimal conditions for all the economic species of the

world and their pests and pathogens. This system,

which could be called the International Plant

Utilization Data Base (IPUD), would answer a multitide of questions and avoid many costly problems.

For example, with this one-time multimillion dollar project, one could prevent many multimillion

dollar mistakes made in introducing the wrong species in developing countries. It could help developing countries develop import substitution programs

which might save them million of dollars. This

might make the country more self-sufficient and

decrease its need for transporting goods.

The perennials growing in remote areas can help

one assess the plants best grown there. The IPUD

could help one map the areas in a country where

a plant introduction is most likely and least likely

to succeed. Ancillary to this should be the development of an economic data base (such as is hinted

at in fig. 12), which includes transportation costs,

shelf life, world demand, trends in production, and

current price of a species, Crops that make the most

sense economically then could be chosen from the

many crops ecologically adapted to the remote area.

All should be tried experimentally before planted

on a large scale. Experimental data resulting from

trials would be used to select the right species for

that particular area and to augment and refine the

data base.

We have developed several prototype files that

could attack big problems systematically. Currently these files are undersupported; we have not yet

convinced international authorities of the value of

an International Plant Utilization Data Base. Such

a data base could reduce international agricultural

trade while improving internal trade deficits accordingly. It could reduce the petroleum used in

international transport of agricultural goods. The

IPUD could select species best adapted to a given

climate for whole-plant utilization schemes in

which food, oilseeds, leaf-proteins, chemurgics,

drugs, etc. would be the main products and biomass

would be an energy-producing or commercial fiber

byproduct. Greater plant use becomes more important as petroleum supplies become more scarce and

expensive.

Implications

Without funding, our data bases now have a life

expectancy of no more than 3 years. The cost of

maintaining our files online is more than $10,000

a year, even before any programs are run on the

data. Are they worth the cost? Who can use them?

The data bases’ contribution to the quest for sorghum tolerant of high alkali soils, a multimillion

dollar problem, already has been cited. Similar

searches for germ plasm suitable to marginal environments might be made for any of the hundreds

of economic species and thousands of medicinal

species. USDA is a constant user; daily it consults

the hard copy generated by the EBL data base to

answer questions on agronomy, agroforestry, climate, ecology, ethnomedicine, nutrition, pathology,

and utilization.

Many other agencies have benefitted from the

files and could reduce future costs by consulting

them,

Agency

AID

APHIS

CIA

Some examples are given below.

Questions We Can Help Answer

What crops are best adapted to Lesotho?

What trees can you recommend for reforestation in Haiti?

USDA, in collaboration with NAS and NIFTAL, is setting up some provenance trials.

What species would you suggest?

Where in the U.S. is niger seed, an ingredient of birdseed, most likely to become a

weed?

Which of the Chinese medicinal plants-e.g.,

honeysuckle, kudzu, and perilla-are most

liable to become weeds around the various

ports of entry?

Where in South America can Erythroxylum

be grown?

File(s)

ECOSYSTEMAT

AGROFOREST

ECOSYSTEMAT

ECOSYSTEMAT

ECOSYSTEMAT

CHINA

CLIMATE

CLIMATE

ECOSYSTEMAT
The USDA Economy Botany Laboratory’s Data Base on Minor Economic Plant Species ● 211

DOD

DOE

FDA

NAS

NIDA

NIFTAL

NIH

NIOSH

OTA

SBA

VITA

Do the trees in the background behind these

maneuvers indicate that this is a tropical,

temperate, or subarctic area?

What trichothecene-like compounds are produced by species tolerant of the Laotian climate?

If our supplies of atropine were cut off, what

would be the best places in the United States

to grow the various species that contain

atropine?

Give us addresses of seed sources from our

allies.

Which herbs grown in Teheran are good

sources of vitamin C?

List the edible and medical species of Iran.

What phytomass yields have been reported

from Panama? What species is the highest

biomass producer reported in your file?

What is the standing biomass of the Republic of Panama?

List the major crops and energy potential of

their residue for 66 developing countries.

What species contain safrole?

We need 100 lb of comfrey root from different latitudes to check out variability in

carcinogenicity.

What is the nutritional value of the neglected

legume species of the world?

Assuming Bolivia, Colombia, and Peru all

phase out coca, where else in Latin America

can it best be grown? What about Cannabis?

Papaver somniferum? What tree crops can

be grown around Chipiriri, Bolivia, where

cocaine production is being discouraged?

What herbs can be grown in the Golden Triangle where they are phasing out poppy production?

What crops can be grown in the peat

swamps of Jamaica, where the ganja is being grown?

What legumes, other than caesalpinoid

legumes, can you recommend for tropical

moist forest, elfin forest, subtropical thorn

forest, and warm temperate rain forest?

What are the medicinal uses of our 44 major nitrogen-fixing species?

Where can we get several tons of winged

bean?

What are the folk anticancer plants of

China?

What carcinogenic compounds are found in

the herbs and spices processed here in the

United States?

List in order of decreasing protein content

the top 100 leaf-protein producers on a zeromoisture basis.

Which would do best in the tobacco belt of

the Carolinas?

Which species could give the most leaf protein per hectare?

What commercial crops can you recommend for the Lake Miragone region of Haiti?

What firewood trees can you recommend

for our site in Ecuador, with a climate identical with that in Quito?

What natural pesticide species—such as

neem, pyrethrum, and ryania—can you recommend for the San Jose area of Costa Rica?

What living-fence post trees produce the

best firewood for Columbia?

CLIMATE

ECOSYSTEMAT

CLIMATE

PHYTOTOXIN

ECOSYSTEMAT

CLIMATE

NUTRITION

GEOGRAPHY

UTILIZAT

PHYTOMASS

YIELDS

ECOSYSTEMAT

PHYTOMASS

YIELDS

PHYTOTOXIN

ECOSYSTEMAT

NUTRITION

ECOSYSTEMAT

CLIMATE

ECOSYSTEMAT

CLIMATE

ETHNOMED

ECOSYSTEMAT

ETHNOMED

PHYTOTOXIN

NUTRITION

YIELDS

CLIMATE

ECOSYSTMAT

AGROFOREST

CLIMATE

ETHNOMED

AGROFOREST

CLIMATE

VISTA What esoteric culinary herbs can you recommend for the climate in Oregon? ETHNOMED

WHO List contraceptive plants. List molluscicidal

plants. ETHNOMED

WRAR What are the medicinal uses of Polygonum

alpinum? ETHNOMED

What antimalarial species grow in Nigeria? ETHNOMED

AID – Agency for International Development

APHIS – Animal and Plant Health Inspection Service

CIA – Central Intelligence Agency

DOD – Department of Defense

DOE – Department of Energy

FDA – Food and Drug Administration

NAS – National Academy of Sciences

NIDA – National Institute of Drug Abuse

NIFTAL — Nitrogen Fixation By Tropical Agricultural Legumes

NIH – National Institute of Health

NIOSH – National Institute of Occupational Safety and Health

OTA – Office of Technology Assessment

SBA – Small Business Administration

VITA – Volunteers in Technical Assistance

VISTA — Volunteers in Service to America

WHO – World Health Organization

WRAR – Walter Reed Army Research

There are partial or complete answers to these

questions in the files of the data base, now off-line.

These are samples representing only a few of the

innumerable possible questions, many of which

have not even been asked, much less answered. The

development and maintenance of an International

Plant Utilization Data Base, an on-line interlocking

system with agronomic, biochemical, climatological, ecological, economic, entomological, geographic, pathological, pedological, and use data on the

thousands of economic plant species, could help answer present and future questions.

Appendix I:

Latin American LocaIities

SuitabIe for Date Palm Cultivation

by Alan A. Atchley*

“The date palm must have its feet in water and its head

in fire, ” goes an old Arab saying. The familiar image of

a desert oasis supporting a grove of these palms surrounded by barren dunes seems to fulfill this proverb,

for the trees are “naturally irrigated” by the waters of

the oasis and their crowns are exposed to some of the

hottest weather in the world. But the oasis draws its water

from the natural rainfall over a wide expense, and the

palms are not independent of the rainfall component of

the climate as they would be under artificial irrigation.

Can modern data processing techniques reveal the climatic tolerances of this important palm species and suggest where it might be introduced successfully? The Economic Botany Laboratory’s methods were applied to find

sites in Latin America where, based on the computerized

information in AEGIS (Agricultural, Ecological, Geographic Information System), date palms might grow successfully. (AEGIS is handled with the SAS programing

● Research Botanist, USDA, ARS, Economic Botany Laboratory, Beltsville, MD

20705.
272 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Figure 12.-Sample Page From Botanical Price Lists

.Uie .s si5erica cil. ... ..$ 8,5(3 - 9. 00/1!2

---- ‘ “ -q -c 3 i ze . ● . . . ● . . ● ..*. ● .*$ 1.02 - 1. lg/1~

>.: 1>-1 ~sothizcyznaze. ... $ ?. 25 - 7. gO/~b

.Cxczi oil. . ● ● ● ● ., . ● .., ,$ 1.2(I - ~ . OQ/1~

All~ . . . . . . . . . . . . . . . . . . . . $ .51 - 1. 50/lb

.*Join . . . ● . . . . . . . . . . . . . . . .s 5.75 - 6. 00/lb

-AATris. . . . . . . . . . ● ●

- 

●

... * $ - 9. ~0/lb

k; tkcle . . . . . . . ● . . . ● ● . . ● $ 2. 50/15

.Ac~eli2a rooc oil. ., ... .$ 80~ . ()()/ lb

$zis e oil . . . . . . . . . . . . . . . $ 11 ● 50 : 13.09/15

.+-~c= ~eeAk. . . ● . . . ● . . . . . ● 7Q 1. <Jo - 1. 60/lb

A“= ricc~ kernel oil. . . . . . $ - 2. 00/lb d- L . - ~~ a- 1 c ~ um. . . . . . . . . . . . . . $ .89 - 1.44 /lb

.~-\-z c Zez oil . . - . . . . . . . . . . $ 1:. og - 4 .Z5/lb

B Q 10.75 - 12. 50/lb ;.. =~~ ● ● . . . . . . . . ● . ● ● . “ “ ~

B:;tb =Y:>* ~“=~. . . ● .... .... $ 2.70 - 3. 00/lb

SzL1223nza leaf. ... ... ..$ 2.40 - 2. 45~lb

~=n ~ a~~ehj-d e . . . . . ● ● ● ● ● ● “ $ 1.24 - 1. 28/lb

r-E: f=.>e . . . . . . . . . . . . . . . . . 4. 50/lb

C:lzus cil. . . . . . . . . . . . . ; : 55.09/1?s

C=p~cr. . . . . ..... .: ..... $ 3.63 - 2. 7!2/ 15

C=p5cr oil . . . . . . . . . . . . . .c 1 ● ~o - 2.25 /lb

r . s LnL7g2 oil. . . . . . ● . . ● ... $ 22.00 - 23. @/~~

Can<elilla wax. ,

c 

. . . . . . . . . 1. ?0 - 2. 10/lb

Ca?sicom oleoxesin.. ... .$, 8.40- 16.50/lb

Csr==~ay nil. ..$. ... ... ..$ 29.00 - 30.00/l b

Car~-~”a:: seed. . . . . . . . . . . . $ -55 - .69 ~ lb

C=r5a=2n . . . . , . . . . . . . ● ● ● “ .s 3.00- 4. 50/lb

c. .

-C~.au;a WZX. . . . . . . . . . . . $ ~o

l ~ - 2. 05/lb

c!-C2 y-~ze. . . . . . .“. . . . . . . . $ - ‘:8.00/lb

l-CZrx x-e. . . . . . . . . . . . . . . $ ~.5Q - 9.75 /~b

Czsczrz zzgz~d=.. . . . . ... $ 1. 00/lb

Qsz iz c . . . . . . . . . . . . . . . . . . .

.67 - . $ofl~

Castor oil. . . . . . ........5 .45 - . 6g/ lb

Czztar po=cc. . . . ● ... ... $ - 13~*5n/t~~

C2:e:k31. . . . . . . . . ... ... .$ 2.94 - 7. 48/!:il:;

CedarlaaS oil. . . . . . . . . ● ● $ logo _ 2. 10/lb

Ced=m-uod cei l . . . . . . .. ..$ 2.35 -

CslerY seed. . . . .

3. Q()/~b

. . . . . . . . $ .46 - .47 /lb

Csl~=Y seed cil. ... ... ..$ 29.50 - 1:5.>5/lb

C~.a=zALe flo-wrs. ... ... $ 3.35 - ~ . 94/13

. .

fl.-=J-3-&le “---- C1l. . ● . . . . . . . . $ -

370. 90/lb

r.-~-~;;~i~~ Oil. . . . . . . . . $ “ . . . . .

11. ()~/1~

Ck.s rq: kernel oil*.*.. ... $ 1.00: ~ ● 4g/llJ

C:nC3=3n. . . . . * . . . . . . . . . . 1 ● 35/lb

cti22zan bark oil. . . . . . .

:2/,0: ;: : 250. 00/kilc

Cim2==2n leaf oil. ... ... $ 2.90 - 3. 00/15

c~:r~~ Xz:ural . . . . . . . ● ● $ 6. ‘)5 /~~

(“’’tr~~~~~a ~8~, ceylo~,.$ 2.ZO - 2.60/lb

-. . T C-Er2..2l3a oll,dava. . . . . .c 3.45 - 4.75/15

CLzr3z51La oil, Chiza. ..$ ?.75/15

c~~r~ae~~a~....a .=. . . . . . $ 4.00 : .6.20/lb

SOURCE:Chemlcal Marketing Reportec 1992.

~l~ronellcl. . . . 4,90 - in.on/1~ - . ● . ““ “ “ “+

cloYe leaf oil . . . . . . . ● ..Ve 1.95 - 4.00/lb

~lOY~ bud Oil. . . . . . . . . . . $ 19.50 - 28.00/lb

rlo...es- , , . . . . . . . ● . . ● ● “ “ . ● $ 5.00 - 5.lo/lb

Coc=inc hj.dro:hlsride.. .$ -900.00/kilo

Cocillana bark . . . . . . . . ..>< .4@ - ,45/15

co?s~:e. . . . . . . . . . . . . . . . . $ -9Q0.fJO/~il~

Co=i~~dez oil.. . . . . . . . . . $ 25.00 - 37.00/lb

Ccri=.nder szed . . . . . . . . . . $ .34 - .41/lb

CCrn Sil... . . . . . . . . . . . . . $ .134- .14/lb

Cottonseed oil. . . . . . . . . .$- .13/lb

Couiirin.. . . . . . . . . . . . . . . $

- 6c~0/~b

Cube root.. ... ... ... ....$ .60/lb

Cu~ene . . . . . . . ..* “. . , . , ● . .$: .23~/lb

Cuin see~ . . . . . . . . . . . . . . $ - 1.03/lb

C;cl:nen aldehyde. . . .... $ - 6.00/lb

>Igzcaxln. . . . . . .

. .

● . . . . . . ● Tc 2.60 - 3.00/gr2m

Dill=eed oil.... . . . . . . . . $ 9.00 - 13.75/lb

F.phedrine. . . . . . . ... .....$ 1.25/oz

-pine?hrfie. ! . . - . . . . . . . .$ :.5!?/gzam ruczlj,;to~= ● ● c - 4eoQ/15 .****.. ● .=*7

Eucal>-pt.Gs oi l . . . . . . . ..,y~ 20Q0 _ 3.10/l b

~ugcno~. r-l . . . . . . . . . . . . . . . . .Yc 3*9O - 4,0~/~~

Fennel ail. . . . . . . . . . . . . . $ - 10.00/lb

~~nn~~ s~ed . . . . . . . . . . . . . $ .57 - 1.07/lb ~oep.ugreek Seed. ... .....$ .37/lb

Carlic Gil. . . . . . . . . . . . . .$: 25.QO/lb

Ceraniol .. . . . . . . . . . . . . . $ ~O()@ _ 1200()/lb

Ccranitc oil. ... .... ....$ 21.50 - 69.75/lb

c~ng~r. . . . . . ... .... ....,$ .46 - . .88/lb

Ulnser cil. .... .... .....$ 24.!?0 - 40.00/15 l-.

Ci~-;zr oleorssin.. . . . ...,*Q - 22.00/lb

~~a;a~=uiz .- oil. .... -....$ 1.15 - 2.Qo/~D

Guaiecol. . . . . . . . . . . . . . . . $ - 2060/15

Cu=ia:vocd ceil . . . . . . . . $ - 2.60/lb P,___ -,-c- :U=. . . . . . . . # . . . . . . . $ .79 - : ,~r;/~’;

uel~o~iop~n, . . . . . . ● . - -

. . ..$ 8.25 - 9.00/l b

2emlock . 011. ...* .*..*. .* $ - 8.oQ/lb

Eenbzne leaves ...*.*. .O,y .55/15

1ncsicol... . . . . . . . . . . . . . ;:2~.)Q/k~lo

~De~ac root . . . . . .* ..*... $ - ~0.~0/lb

JLjo?2a oil. .... ... ......$ 90.00 -lOC1.00/gal

~=ni;er ~erV o~l.......$ 55.oo - 65.@O/lb

?kra;-a S:O. . . . . . . . . . . . . . $ 1.75 - 2.On/lb

Kola Zucs. . . . . . . . . . . . . . . $

,69 - ,65/lb

Laurel Ie=ves. . . . . . . . . ..$ .52 - .85/15

Lavantin ceil . . . . . . . . . . . $ 50~5 _ 7Q50/lb

Laveadzr flowers . . . . . . . . $ .65 - .75/lb

~av~~~~r flobwr Od‘1 ..*P- $ 11.75 - 15.45;lb

Lemn oil, #.rgcntina. ...$ 6.50 - 7.00/1 5

Lezongrzss oil c . . . . . . . ...y g,]j/ki.1~

~i~orice :OOS. ... .....O .$ ● 4Q - .g~/llJ
The USDA Economy Botany Laboratory’s Data Base on Minor Economic P/ant Species ● 273

language on the computer facilities of the Washington

Computer Center.)

First, locations for which date palm has been reported

were retrieved and their climate parameters analyzed.

The result is the range of climates which would be

searched for; only 13 locations report date palm at present and the application of statistical methods is only suggestive of the palm’s ecological tolerances and not definitive.

The arithmetic means of several climatic parameters

for our small sample of stations suggest that ecological

optima for date palm are approximately: average annual

precipitation ca. 1,000 mm, average annual temperature

ca. 23 “C. Seasonality of the infrared optimal climate is

not apparent from arithmetic means, but the minimum

values for monthly rainfall and temperature suggest a sustained warm summer (temperature 21°C or higher for

each month) and a coldest month with an average

temperature not less than 8°C. Precipitation peaks in the

spring and autumn and a driest-month average precipitation of 4 mm suggests that a dry period is required, and

appears to coincide with the temperature minima.

To select candidate climates from our climate file

which contains data for more than 18,000 meteorological

stations around the world, several assumptions were

made based on the information above. This illustrates

how AEGIS can be used to approximate the potential

range of a given crop based on some knowledge of the

crop and within the limits of reliability of the data from

the file containing known distributions. First, stations

were selected that had an average June temperature figure in excess of 20 “C, a January temperature figure not

less than 8°C, a July precipitation figure not less than 6

mm, and a continentality (Conrad’s index) between —8

and 31 mm (the range found for those stations reporting

date palm), This yielded 862 stations, many in Latin

America. As some of these were found to be characterized by sustained rainfall throughout the year, additional

constraints were added to improve the seasonality match:

either the February or July precipitation was not to exceed 10 mm (for Southern and Northern Hemispheres,

respectively), and the annual average precipitation was

not to exceed 1,500 mm. (The minimum reported for date

palm was 140 mm.) This generated a printout of 125 stations, including the following in Latin America:

Brazil: Araquai. Ecuador: Milagro, San Cristobal, Portoviejo. Guatemala: Amatitlan, Castaneda, Guatemala

City. Honduras: Comayagua, Tegucigalpa. Mexico:

Abasolo, Acaponeta, Ahome, Alcozauca, El Burro,

Calaya, Carbo, Carrillo, Cerritos, Chiautla, Cintalapa, Colima, Comonfort, Concordia, Coguimatlan, Cuautla, Cuernavaca, Dolores Hidalgo, Ejutla, La Esperanza, Etla, Flor

de Jimulco, Gongorron, Guayamas, Huajuapan, Ixmiquilpan, Jonacatepec, Lagos, Lerdo, Manual Doblado, Mezcala Isla, Miahuatlan, Monte Puerta, Moroleon, Motozintla, Nazas, Piaxtla, La Providencia, Puente de Ixtla,

Rioverde, El Rodeo, San Bias, S. J. de Guadelupe, San

Marcos, San Carlode de Yautepec, San Miguel Allende,

Santiago Vane, Sierra Mojada, Tamazula Giordano, TaxCO, Tehuacan, Tlacolula, Toliman, Topolo Bampo, Tuxtla Gutierrez, Union de Tula, Ures, Zimapan, Zinapecuaro, Ameca, Guadalajara, Leon, Oaxaca, Penjamo, Salvatierra, Zamora. Venezuela: Barquisimeto, Guigue,

Valencia.

If more time were available for this quest, the selection process could be refined by entry of more data on

the actual occurrence of date palms correlated with

weather stations, and particularly on the yield of the

palms at such places. At present AEGIS has no yield data

at all on date palms, though published reports surely exist. Such data would help decide whether the palms

would do well, rather than merely survive, at the stations

indicated above. Other refinements, such as better attention to the reversal of seasonality in the southern hemisphere, could improve this kind of approximating retrieval and, in the present case, probably increase the listing

for Brazil.

Appendix II:

Rating American Localities

Suitable for Date Palm

by James Alan Duke

Rather tardily, I am responding to a request to identify localities in Latin America best adapted to the date

palm. I am passing on some of the data to demonstrate

methodology (with a copy to OTA, which requested that

I prepare a paper on applications and uniqueness of our

data base here in EBL).

First the caveats! I have intentionally devoted less than

4 hours to this question. I have asked Dr. A.A. Atchley

of this lab to devote a similar amount of time but to use

his own devices. I hope that some of our conclusions will

be the same! One should devote 4 months, not 4 hours,

to a feasibility study such as this. What we will both send

you are approaches at climatic analogues, very crude

ones at that,

Once analogous climatic stations are uncovered, soils,

availability of water for irrigation, peculiar atmospheric

conditions (such as the fogs in the Chilean-Peruvian desert), and many other factors must be assessed as well.

Here is a thumbnail sketch of some of the date palm’s

peculiar ecological “whims”:

It is very tolerant of alkali soils and can grow in soils containing 3 to 4 percent white alkali, but to bear well, the

palm’s roots must be in a stratum with less than 1 percent

of alkali silts.

Grown ideally where the permanent water table is within

9 to 16 of the soil surface. At least 8 to 9 acre feet of irrigation water per year is necessary for good production

on bearing palms.

Daytime temperatures of 50° C are tolerated. For proper

ripening of fruit, the mean temperature between the period

of flowering and ripening should be above 21.20 C rising

to 26,70 C for at least a month.

Finest date varieties require 3,300 units of heat, a unit being defined as a degree above a daily mean of 64.40 F between the flowering, fruit development, and ripening periods.
214 . Plants: The Potent/a/s for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Israelis blame some of their problems on inability to

control flowering time (it takes 6 months for fruits to

ripen). There can be some control by withholding irrigation during fall and winter. There must be no rain during flowering time. An average temperature of 30° C is

good for proper ripening. Winter temperatures below

–80 C (ca 170 F) are harmful.

Any good soil that is not too heavy will do. In clean

soil, a little hard water is acceptable; but a combination

of alkaline soil and salty water is too much. Dates do well

even where there is a crust of salt on the soil surface.

If, in the top 2 to 2.5 m, there is a 30 cm layer or strata

with 1 percent alkalinity, the date roots will “find” the

strata and flare out there.

Indio, Calif., has long been a center for study of American plant introductions of the date palms. The Indio station is rumored to be in jeopardy, considered by some

as excess government property, at least in part. Jim Carpenter (714-347-3414) should be consulted. He is one of

America’s leading experts on date palms. He could probably point out flaws in this 4-hour document. However,

we are proud of our ability to identify rough climate

analogues, once the specialists tell us what is required.

The following places are reported to produce good date

palms:

ECOSYSTEMATIC ECOSYSTEMATIC

Place Code Plac e Code

Aswan, Egypt . . . . . . . . . 0026 Yuma, Ariz. . . . . . . . . . . . 0122

Fayum, Egypt . . . . . . . 0021 Beer Sheba, Israel ... , . . . . 0219

Ciza, Egypt . . . . . . . . . . . 0020 Bagdad, Iraq. . . . . . . . . . . ., 0123

Thermal, Calif. . . . . . . . . 0123 Basra, Iraq ., , . . . . . . . . . . 0224

Mecca, Calif. ., . . ., . . . 0121 Alexandria, Egypt . . . . . . . . 0220

Indio, Calif. . . . . . . . . . . 0123 Tempe, Ariz. . . . . . . . . . . . . 0220

The first two digits of the ecosystematic code correspond to annual precipitation rounded off to the nearest

decimeter. The second two digits correspond to annual

mean temperature rounded off to the nearest 0 C. Monthly totals should also be consulted in a more refined

feasibility study,

One can then look for comparable examples in a Table

of Ecosystematic Values for Mexico and see that Baja,

California, has several localities with identical ecosystematic codes to those for some of the better date producing localities–e.g., Comondu is analogous to Bagdad

and Indio, Magdalena to Yuma, etc. Based on annual climatic averages alone, one might consider Comondu or

any other place in Latin America with a ecosystematic

code of 0123 to be a possible target for date palm cultivation. Several places in Peru (e.g., El Alto, Bededero,

Campo de Marte, Cayalti, Talera, Trujillo, Zorritos, etc.)

have ecosystematic codes similar to some of those listed

above and could be investigated as date palm targets,

This is just a superficial sketch. While I would bet on

the Baja, California, stations, I would be leary of fog in

Peru (unless hand pollination were guaranteed) and in

all cases I would question the availability of irrigation

water equivalent to 2,300 mm/year.

1.

2.

3.

4.

5.

6,

7,

8.

Roforoncos

Brown, S., and Lugo, A, E., “ The Storage and Production of Organic Matter in Tropical Forests and

Their Role in the Global Carbon Cycle,” Biotropica

14(3); 161-187, 1982.

Coulson, J. R., Chief, Beneficial Insect Introduction

Laboratory, USDA (ARS), Beltsville, Md., personal

communication, 1982.

Council of Scientific and Industrial Research (CSIR),

The Wealth of India, CSIR, Delhi, India, VOIS 1-11,

1948-76,

Duke, J. A., “The Guest for Tolerant Germ Plasm,”

ch. 1, pp. 1-61, ASA Special Symposium 32 “Crop Tolerances to Suboptimal Land Conditions, ” American

Society of Agronomy, Madison, Wis., 1978.

Duke, J. A., Handbook of Legumes of World

Economic Importance (New York: Plenum Press,

1981).

Duke, J. A,, “The Quest for Iron-Efficient Germ

Plasm,” J. of Plant Nutr. 5(4-7): 637-638, 1982.

Gohl, B., Tropical Feeds, FAO, Animal Production

and Health Series #12, FAO, Rome, 1981.

Miller, B, F., “Composition of Cereal Grains and Forages, ’’” NAS Publication #583, National Academy of

Sciences, Washington, D. C., 1958.

9. att, B. K. and A. L. Merrill, “Composition of Foods,”

Agriculture Handbook No. 8, USDA, Washington,

D. C., 1963.

10. Wernstedt, F. L., World Climatic Data. (Lemont, Pa,:

Climatic Data Press, 1972).
ECOLOGICAL PERSPECTIVE ON THE INCREASING USE OF PLANTS

TO PROVIDE USEFUL PRODUCTS

(A Review of the OTA Workshop 

Richard R. Harwood

Rodale Research Center

Kutztown, Pennsylvania

Introduction

Breadth of ecological implication

The suggested broadened use of the world’s plant

resource base has ecological implications which are

considerably more far-reaching than those implied

by most alternative technology choices. These potential ecological impacts should be considered as

underscoring the significance of this OTA study.

In the eyes of at least one analyst (14), the

mechanical-industrial age of the late 1800’s and early 1900’S gave way during the 1940’s to the age of

alchemy. We have learned to synthesize innumerable useful products from raw materials. In some

instances those raw materials are readily available

and seemingly inexhaustible. However, a large proportion of our technological efforts are directed

toward developing products from raw materials

that are in finite supply—in particular, fossil hydrocarbons. The age of alchemy seems to have been

characterized by a narrowing of our technological

vision.

In recent years, unlocking genetic codes and developing techniques for cellular manipulation of genetic materials have renewed the interest in developing biological processes and materials to create

products useful to humankind. These new techniques may provide the transition tools to take us

from the age of alchemy to that of algeny, in which

there would be a greater reliance on biological

rather than nonliving, chemical processes. It seems

that the energy and resource consumption of the

chemistry-based technologies of today are nonsustainable. In addition, the environmental loading of

slowly biogradable or nonbiodegradable materials

has adverse implications for the quality of human

life and for native flora and fauna.

Many people are not aware that the new biotechnologies are as dependent upon the availability of

existing genetic material as they are on raw materials. For the foreseeable future, we will depend primarily upon existing life forms rather than on artificially synthesized life constructed according to

design from some sort of “basic building blocks.”

The new technologies enable the rather rapid shaping and molding of existing genetic material into

more productive and useful forms. The identification of those potentially useful biological materials

is the focus of work surveyed in this study.

Far-reaching issues Of direction

and paradigm

The present dependence on a limited number of

plant species as sources of most of our raw products and food permits use of only a small fraction

of the Earth’s surface for production of useful products. The demand for those products often outstrips

the productive capacity of the “arable” land used

to produce them. As our technologies focus on an

ever-narrowing list of commercial crops for food,

fuel, fiber, and industrial products, and as growing demand forces greater production of these few

commodities, there is increasing evidence of adverse environmental impact and a subsequent decrease in our production resource base. Nonsustainable levels of soil erosion or ground water

depletion are evidence not only of deficient production technologies but also of growing crops that are

too resource-demanding. Forcing corn, wheat, soybeans, or other annuals onto land that will not sustain them is a short-term solution to product supply.

The vast areas of land now considered to have

low production potential for the present intensively cultivated crops maybe considerably more productive with carefully selected and properly managed alternative crops. Many lands which are now

commercially unproductive could be cropped safely to a wide range of perennial crops identified as

sources of useful products. Jojoba and sisal for

semiarid environments are excellent examples.

There are also many potentially valuable biocidal

compounds produced in species adapted to semiarid environments. These marginally productive

environments (as measured by their ability to produce our current major annual crops) typically are

areas of environmental degradation and human

poverty. Broadening our crop focus and making use

of potential production resources could help arrest

resource deterioration and improve the quality of

life in these areas.

Benefits of using biologically

produced materials

One of the adverse effects of “the age of alchemy”

has been the environmental loading of synthetic

materials, particularly biocides. While biologically produced materials may have equally disruptive

short-term effects, they are biodegradable and rare215
216 • Plants: The potentials for Extracting Protein, Medicines, and Other Useful Chemicals—WorkshoD Proceedings

ly persist over long periods, so cause little, if any,

long-term disruption. Once having identified such

compounds, it is often possible to synthesize them.

In the case of the insecticide pyrethrum, however,

insects have not built up a resistance to the naturally occurring form, but they have to the synthetic:

form (2,4).

A disadvantage of relying on plant-derived biocides is that they seldom have narrow selectivity

and do not move systematically in plant tissue,

They can be used near the time of harvest, however,

because of their short residual time.

The importance of genetic diversit y

Much has been written in recent years on the subject of crop diversity. The widespread incidence in

the United States in 1970 of corn leaf blight, which

caused an estimated 15 percent loss of our corn

crop, aroused considerable interest and concern.

The National Academy of Sciences’ study “Genetic

Vulnerability of Major Crops” (5) became the

benchmark to a series of subsequent reports. The

report’s primary recommendations focused on increased emphasis on plant breeding and improved

germ plasm collections, Subsequent NAS reports

have dealt with the desirability of increasing the

world’s crop base (6,7,8,9,10,11,12). There continues to be considerable alarm over decreasing

crop genetic diversity (15). Increased crop diversity reduces the buildup and spread of plant pathogens and insect pests. From the standpoint of the

individual farm, a variety of crop options vastly increases the economic stability of the operation and

provides the “tools” needed to structure a resourceefficient operation. The vast array of crops grown

on a typical Chinese vegetable farm nicely illustrates the point (3). Having an array of crop options

permits the establishment of rotations to reduce

cost of controlling weeds and soil-borne insects and

diseases.

The energy saving of greater self-reliance

The identification of plant sources for industrial

products, pharmaceuticals, and pesticides would

have a positive impact on developing countries. In

some cases the new crops could provide the basis

for a new export industry, but the greatest impact

would be to permit a greater degree of self-reliance

Having a greater capacity for in-country production of raw materials rather than a worldwide network of product flow with highly centralized synthesis and distribution reduces the service, handling, shipping, and, ultimately, the energy costs of

a product. In the future energy-and-resource-limited world, a new balance between production and

service costs must be reached. We will no longer

be able to afford the energy-intensive open supply

loops of the past (1).

The USDA Economic Botany

Laboratory's Data Base on Minor

Economic Plant Species

by James Duke

Much, if not most, of our crop movement and related agricultural development work over the past

several decades has, ironically in an age of computer and systems science, been done empirically

(3). The USDA’s data base on minor economic

plants, if extensively used, would help match crops

to their “best fit” environment. It would assist

significantly in development planning by suggesting the best crop options for target environments

and by helping to minimize crop development efforts in environments that are marginal or unsuited

to the crop species. Marginal environments typically mandate the use of extreme measures, either in

modifying the environment or in protecting the

crop. Under stress conditions, most crops are more

sensitive to a pest or pathogen. A “best fit” cropenvironment situation generally leads to optimal

crop-environment biological stability with minimal

need for drastic intervention with biocides or other

harmful production inputs or technologies. The

ecosystematic file described by Duke has potential

for the greatest positive environmental impact of

all technologies discussed in this workshop.

The USDA data base can play an important role

in dealing with the spread of pests or diseases. Plant

scientists recognize the need for extreme caution

when moving plant materials. There are elaborate

protection mechanisms to safeguard against the

spread of pests and diseases. The recent movement

of the Mediterranean fruit fly to California is an example of a detrimental introduction. In all likelihood this pest was introduced through transporting

produce rather than plant genetic material. One

finds, however, that when dealing with “exotic” or

noncommercial plant species, the normal plant

quarantine coverage often is less stringent than

with commercial species. If a little-known species

does not appear on the list of “regulated” species

in a country, it often can be moved in or out freely. Most scientists, in their concern for making rapid progress, hope for ease of moving materials, despite the dangers. It seems that the present U.S.
Ecological Perspectives on the Increasing Use of Plants to Provide Useful Products . 217

quarantine laws with respect to movement of seed

and plant materials are adequate, but budgets, staff,

and facilities are not adequate to accomplish much

more than perfunctory formalities.

There is one further consideration concerning the

biological stability of materials moved to different

environments. The USDA’s ecosystematic file is

based on environmental classification according to

various factors of the physical environment. The

species composition of the plant flora constitutes

a second order of classification. As Dr. Duke suggests, this helps define environments where a given

species can be expected to perform well. However,

more attention should be paid to the pest/pathogen

balance of a species. If a species has inhabited a

given environment for decades or centuries, it and

its pests and pathogens can be expected to have coevolved so they are in relative equilibrium. That is

not the case with a species introduced into an environment that is physically similar. Even if the introduced seed or plant material has left behind its

complement of pests and pathogens, in all likelihood some of the insects or pathogenic organisms

in the new environment will be able to use it as a

new host. There is little, if any, way to predict or

guard against such occurrences with information

available today. Such unknowns should not impede

crop movement, but the crop should be carefully

monitored in its new environment. The USDA Economic Botany Lab’s pest file could be helpful in providing information relevant to crop introductions,

especially if the file is expanded to record the ecological amplitudes of pests and diseases.

In light of the potential of the USDA data base

for providing long- term environmental benefits,

the lack of sufficient funds and the inactivation of

such a useful and beneficial program ar e

regrettable.

information Gathering and Data

Bases That Are Pertinent to the

Development of Plant-Derived

Drugs

by Norman Farnsworth

and William Loub

Most of the comments on the Duke paper apply

equally to this work. The desirability of diversifying our agricultural crop base supports any efforts

leading to that end. Despite the wide ranging potential benefits of developing plant species for pharmaceutical extracts, U.S. pharmaceutical companies show little interest in this field.

Farnsworth and Loub state that “typical industrial drug development has increasingly involved

synthesis of molecules based on structure-activity

relationships” and that “not a single pharmaceutical manufacturer in the United States is involved

in a research program to discover new drugs from

higher plants.” This pattern is also followed by

companies developing agricultural biocides,

The major ecological problems in researching

and developing pharmaceuticals from plants involve the movement of plant materials and depletion of natural sources of diversity. In the screening phase, it is usually desirable to collect plant

materials directly from their native habitat for laboratory processing, extraction, and testing to save

money and time. Where materials are to be used

for laboratory processing, precautions must be

taken to minimize the danger of spreading unwanted organisms. This requires constraint on the

part of the research laboratory to avoid replanting

materials not screened for propagation, Once a species is identified as having potential, however,

greater quantities of material are needed for more

extensive extraction and testing, The extent and

amounts of the species should be evaluated before

extensive and voluminous collecting is done so as

not to deplete existing genetic diversity. This could

severely limit future breeding work. Likewise, once

a useful product is known and commercial extraction begins, agricultural production of the species

must be started if the species is not plentiful in the

wild. A high price for a raw product of a wild species can quickly drive the species to extinction. This

is true for the entire range of useful plant products,

particularly those of high value.

An Alternate Use for Tobacco

Agriculture: Proteins for Food Plus

a Safer Smoking Material

by Samuel Wildman

An overriding issue in the development of tobacco is the desirability of subsidizing research and

development of a crop that has a large economic

demand but few socially redeeming features to balance its high social costs.

The crop has severe adverse environmental impacts. When grown in the traditional manner, it

quickly reduces the natural soil fertility. The many

field operations, including cultivations and vehicular and field worker traffic, lead to compaction and

deterioration of soil structure. The soils of the

warm, humid tobacco areas are subject to erosion.

24-503 0 - 83 - 15
218 ● Plants: The Potent/a/s for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

These problems could be alleviated by growing tobacco in a carefully planned matrix of cover crops,

rotations, and limited tillage systems, so they are

not necessarily overwhelming. Of even greater concern are the large quantities of chemical inputs

needed for field production.

It is argued that biomass production reduces the

need for insecticides. The 10 to 12 sprayings required for a crop of smoking tobacco can be reduced considerably if processing for protein extraction

can avoid the “cosmetic” quality restrictions of

whole-leaf tobacco. The problems of seedling establishment require either “clean” or previously unused land or fumigation. Fumigation is an extremely environmentally disruptive process. Depending

on the materials used, the presence of the chemical

fumigant can be of short duration, but the disruption of soil microflora and microfauna is longer

lasting. The alternative of transplanting requires

less area in seedbed but higher costs of growing and

handling the transplants.

From any standpoint, tobacco is an energy-intensive, fertilizer- intensive crop with high environmental impact. A saving factor under present practice is that commonly it is grown in relatively small

fields because of the allotment system and labor requirements. This mitigates its adverse effects to

some extent. It is conceivable that the more concentrated area production necessitated by a processing facility would present greater environmental problems.

An energy analysis of tobacco production and of

its leaf protein extraction should be accomplished

before much more work is done. In the long term,

energy costs closely parallel dollar costs. There

must be crops that could produce equal quality leaf

protein at considerably lower cost. From an environmental standpoint, it seems that the greatest

contribution of a tobacco leaf protein industry

would be to decrease tobacco acreage.

The statements in Wildman’s text that “agriculture in developing countries in the, tropics is notable for lack of crops of high protein content” or that

“soybeans also cannot be grown in the tropics” simply are not true. Tobacco, in fact, has increased pest

problems in tropical environments so that it is even

harder to grow it.

Loaf Protein Extraction From

Tropical Plants

by Lebel Telek

The work of screening tropical plant materials for

protein content, fractionation properties, and evaluation of the resultant protein fraction is environment-neutral. Telek’s paper points out nicely, however, the complexity of production systems required for effective use of protein extraction technology. With production of standard human food

or animal feed-grade protein, the integration of several industries is essential. The complexity of interactions between those industries and the environment render a simplistic summary of environmental impact of little use. The following types of

analyses of each industry segment maybe required

for any particular environmental zone of production:

1.

2.

3.

4.

Raw product production impact—energy cost,

environmental impact of the crop production

(soil loss, ground water use and impact, biocide

requirements and impact);

Raw product quality—the production-related

materials that may be present to contaminate

the protein and product;

Extraction process impact—energy requirement; cost of holding air- and water-effluent

discharges to acceptable volume and quality;

cost of solvent recycling or disposal;

Impact of related industries that use various

plant fractions.

At this early stage in the development of plant

protein isolation processes, an analysis of energy

efficiencies of alternative protein use pathways

would be in order. Comparing whole-plant use by

various fish and animals with fungal or bacterial

digestion would give rough estimates of threshold

energy efficiencies that must be achieved by fractionation systems in order to be competitive. As far

as possible in these analyses, it is essential to internalize the costs for avoiding environmental disruption. Conservative estimates by today’s standards of permissible environmental loading would

be appropriate if the model is to be applicable in

the future. Such analyses will be complex and costly and should not be required for each enterprise

being considered. Such analyses would be useful

at this early developmental stage to provide guidelines and estimates of the practicality of a given

pathway. Few data are available, and energy and

cost effectiveness of the fractionation methods are

difficult to assess.

Third World production of many, if not most, of

the species tested—particularly the perennial

crops—presents no environmental problems not already well recognized for those species. Given a

choice, one would prefer to grow the crop requiring the lowest nonsolar energy input and having

the greatest amount of stability with respect to pest

and disease incidence.
Ecological Perspectives on the Increasing Use of Plants to Provide Useful Products .219

Insecticides, lnsect Repellants,

and Attractants From Arid/Semiarid

Land PIants

by Martin Jacobson

With increasing emphasis on integrated pest

management, there is increasing opportunity to use

a wide range of materials affecting insect behavior.

Because many of these materials seem to have

evolved to a greater extent in arid/semiarid plants,

a search for such compounds could be productively targeted at these plants. It is unfortunate in that

production in such environments on a commercial

scale must be carefully managed with respect to

ground water use and soil conservation. As with

all other plant-derived products, the recycling or

disposal of solvents used in the process is important.

The areas of plant-derived biocides and insect behavior modifying compounds has potential for having a significant impact on the ecological effects

of modern agriculture. Many of our present synthetic biocides are extremely persistent in the environment, and their accumulation is the source of

considerable concern.

An example is Temick, an insecticide that has

been used by many Long Island potato growers

against the Colorado potato beetle. Because of its

persistence it has leached through the sandy soils

of Long Island to reach ground water aquifers in

relatively high concentrations. In years past a

material comprised of ryania, rotenone, and pyrethrum—all plant-derived insecticides—had been

used with equal effectiveness. Its use was discontinued because of the lower cost of Temick and

other synthetic materials. An effort is under way

to bring back the plant materials to replace Temick.

With the exception of pyrethrum, a commonly

used household insecticide, the work on commercial use of plant insecticidal materials has been

limited to small companies specializing in “alternative” agricultural products. Little indication exists of industry interest in such products, a situation analagous to that of the pharmaceutical industry.

A wide range of insect-behavior-modifying substances that have little biocidal activity exists in

plants. Work at Rodale Research Center shows that

camphor, a compound present in many aromatic

plants, has strong insect-repellant activity. Camphor wood, in fact, has been used from ancient

times because of its durability. Little work has been

done to identify such compounds. These compounds, along with plant-derived insecticides,

could have a positive and widespread impact on

agricultural systems by replacing many of the more

environmentally disruptive materials now commonly used in agricultural production.

Environmental impact studies should be conducted for plant-derived pesticides. Most botanical

are nonselective but of relatively short persistence.

Molluscicidal and Other Economic

Potentials of Endod

by Aklilu Lemma

Ended has broad-spectrum biocidal activity as a

molluscicide, spermatocide, insecticide, and bactericide. Here, again, the range of its effects should

be studied before it is used widely in the United

States. Its effects on humans, wildlife, fish, and a

broad spectrum of biological organisms likely to be

affected by common application should be determined. The research detail and resultant cost for

this work seem to necessitate the creation of patent

rights and protection which would make the expenditure attractive to industry. Government support in the form of research funding may also be

essential.

Each of these potential crops should be included

in a refined USDA data base on minor economic

plants species, and their likely growing areas

should be determined before a major research commitment is made. If a species has fairly broad production area potential, it would be a more attractive investment.

The Role of the Alkaloids of

Catharanthus Roseus . . . .

by Gordon Svoboda

Many of the points raised previously apply to this

paper. They are the:

1. need for careful collection of the crop in the

wild prior to production;

2. need for caution in moving plant materials;

3. need for analysis of recycling or disposal of

production solvents and chemicals; and

4. potential for residues of production chemicals

to find their way through the extraction process.

The energy cost of such extraction is less relevant

because the product is of low volume and high

value.
220 . Plants: The potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

The production impact should be monitored;

however, with extremely small acreage the production is relatively easy to frame within production

of rotation crops and other environment-protecting

practices. A significant adverse environmental impact from crop production is unlikely.

Chemicals From Arid/Semiarid

Land Plants: Whole Plant Use

Of Milkweeds

by Robert Adams

Most of the previous comments relevant to dryland agricultural production apply here. The dry

areas where milkweeds have been tested commercially are very prone to erosion. In evaluating the

production costs, it will be necessary to factor in

conservative erosion control practices from the

start. Zero till, crop overseeding, sod culture, narrow strip cropping, and a range of other options

should be evaluated. In the near future solutions

to erosion problems must be found. Those solutions

will have associated costs which will have to be included in the crop production cost.

The potential of milkweed or similar crops as

weed pests should be evaluated. Nevertheless, milkweed, with its potential as a dryland crop in a low

rainfall area, might be able to replace irrigated

crops in areas now experiencing ground water depletion.

Marine Plants: A Unique and

Unexplored Resource

by William Fenical

This area of study is quite different from those

of terrestrial plants. Areas of environmental concern include:

1. The undesirability of studying “fragile” marine

organisms for potential use. For instance,

species of coral that are limited in extent and

slow-growing probably could not be used effectively even if they contained useful compounds. The studies should be limited to those

that are either relatively plentiful or not too difficult to culture.

2. The Presence of contaminants in the marine

environment can be a limiting factor for some

species or products if they are difficult to remove in the fractionation process.

1.

2,

3.

4.

5.

6.

7,

8.

9.

10.

11.

Edens, T., and Koenig, H., “Agroecosystems Management in a Resource-Limited World, ” Bio Science

30:10, 1980.

Forsyth, A., “Flower Power Reconsidered,” Harrowsrnith 6(1):44-51, 1981.

Harwood, R., Small Farm Development: Understanding and Improving Farming Systems in the Humid

Tropics (Boulder, Colo.: Westview Press, 1979).

MacIver, D. R., “Natural Insecticide Has Many Advantages,” Agrichem Age, 30, 77, AugustlSeptember,

1982.

National Academy of Sciences, “The Genetic Vulnerability of Major Crops, ” Committee on Genetic Vulnerability of Major Crops, Washington, D. C., 1972.

National Academy of Sciences, “Underexploited

Tropical Plants With Promising Economic Value,”

Washington, D. C,, 1975.

National Academy of Sciences, “The Winged Bean,

A High Protein Crop for the Tropics, ” Washington,

D. C., 1975.

National Academy of Sciences, “Making Aquatic

Weeds Useful: Some Perspectives for Developing

Countries,” Washington, D. C., 1976.

National Academy of Sciences, “Leucaena: Promising Forage and Tree Crop for the Tropics, ” Washington, D. C., 1977.

National Academy of Sciences, “Guayule: An Alternative Source of Natural Rubber, ” Washington, D. C.,

1977.

National Academv of Sciences, “Tropical Legumes:

Resources for the”Future,” Washing~on, D.C~ 1979.

12. National Academy of Sciences, “Firewood Crops:

Shrub and Tree Species for Energy Production,”

Washington, D. C., 1980.

13. Plucknett, D. L., and Beemer, H. (eds.), Vegetable

Farming Systems in the People’s Republic of China

(Boulder, Colo.: Westview Press, 1981).

14. Rifkin, J., Algeny (New York: Viking Press, 1983).

15. Shapiro, M., “Seeds of Disaster,” MotherJones 12-15,

36-37, 1982.
POTENTIALS FOR EXTRACTING PROTEIN, Medicines,

AND OTHER USEFUL CHEMICALS FROM PLANTS:

SOME SOCIOLOGICAL OBSERVATIONS

(A Review of the OTA Workskop Papers)

Frederick N. Buttel

Department of Rural SocioIogy, Cornell University

The extraction of useful chemicals from plants

has a number of potential benefits from a sociological perspective. The major societal benefits would

include substitution of domestically produced commodities for petroleum and other imports, thereby

alleviating balance of payments problems; more

productive use of resources, particularly in marginal farming areas; and diversification of the U.S.

agricultural system, which would permit market expansion without farmer dependence on increasingly expensive and politically problematic Federal

subsidies from traditional commodity programs.

Some degree of government subsidy and other

forms of intervention probably will be required to

stimulate farm- and industrial-level plant extracts

industries, Such government intervention may be

greatly preferable to export subsidies for foodgrains, feedgrains, and other agricultural commodities in light of problems of aggravated balance of

payments deficits and the farm recession.

This paper addresses sociological aspects of plant

extraction in the United States and its agricultural

industry. The paper is organized into six sections.

The first provides some general comments on the

socioeconomic context of efforts to develop plant

extract industries. The second discusses constraints

, on plant extract development relating to the land

resource base, The third is devoted to research and

development (R&D) activities necessary to undergird commercial scale plant extract industries. The

fourth and fifth examine possible impacts of plant

extract development in terms of the organization

of agricultural production and the organization of

nonfarm industry, respectively. The final section

explores various policy and political issues that

have or may emerge in stimulating an expanded

plant extract industry in the United States.

The Current Socioeconom ic

Environment for Developin g

Plant Extract Industries

All 10 papers presented at the OTA workshop

support the expansion of plant extract industries.

However, it is essential to recognize that the present economic era is not entirely propitious for the

types of initiatives proposed in the papers. Thus,

a realistic view of potentials for extracting proteins,

pharmaceuticals, biocides, and other useful chemicals from plants must be tempered by a variety of

conditions that constrain industrial development

in general and that of plant extracts in particular,

The dominant feature of the contemporary

United States and world economy is global recession. That the recession has been and continues to

be global reminds us that all manner of magical

cures for national economic ills must be taken with

a grain of salt and that we must view the situation

more broadly as a fundamental point of global economic reorganization. It is crucial for policymakers

to recognize that the conditions of the post-World

War II economic boom are unlikely to be replicated

and that policies for the 1980’s must reflect new

socioeconomic realities. This is both promising and

discouraging for plant extracts. Much of the thrust

behind stimulating the plant extracts industries is

“import substitution. ” The character of trade relations in the new economic order that will emerge

during the late 1980’s* will make it attractive to

substitute domestically produced substances for

chemicals and raw materials that we have imported

during the past several decades. At the same time,

however, the very conditions that characterize a

recession—capital scarcity, fiscal crisis, economic

uncertainty, rigidities in public policy—make it

more difficult to expand new industries rapidly.

Capital scarcity will certainly be a key constraint

to widespread development of plant extract industries. “Real” interest rates (the nominal interest rate

less the rate of inflation) remain at levels unprecedented during the post-World War II period, despite recent declines in the prime rate. High interest

rates make it much more difficult for new industries to attract capital and greatly increase the riskiness of new ventures with uncertain markets and

production technologies.

● These trends will likely involve: 1) further decline of traditional U.S.

manufacturing industries (e.g., autos, steel) and increased competition

with the firms of foreign countries (especially Japan, South Korea,

Taiwan, Singapore, and Hong Kong), and 2) an eventual tightening of

markets in petroleum and other raw materials. These two trends suggest continuing balance of payments problems, making import substitution industries such as plant extracts quite attractive.

221
222 Ž Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

In addition to capital scarcity, economic recession involves several other conditions adverse to

expansion of new plant extract industries. First, the

recession’s downward pressure on inflation rates,

especially when combined with restrictive monetary policy in the United States, tends to make imports cheaper relative to domestically produced

commodities. Thus, to the degree that plant extract

industries involve import substitution, they will be

attempting to produce commodities domestically

that have been imported at a time in which a strong

U.S. dollar lowers the relative price of these imports. This has been the case particularly for fossil

fuels and other raw materials, against many of

which domestically produced plant extracts would

compete. Raw material prices are heavily influenced by the level of demand, which in turn is heavily influenced by general economic conditions. For

example, declining energy demand has led to dramatic declines in the real price of energy, which

now is only slightly higher than before the Arab Oil

Embargo of 1973-74. Global economic recovery,

which is likely to proceed slowly over perhaps a

5-year period, will lead to a tightening of oil and

other raw materials markets and will than cause

rapid increases in relative prices of these raw

materials some years later. However, the fact remains that plant extracts that compete against imported raw materials or industrial feedstocks must

temporarily buck an otherwise strong logic of increased import dependence on raw materials. Wise

policy makers will recognize, however, that raw

materials markets will tighten over the next decade

and that the most desirable time for front-end R&D

and other subsidies for the development of plant

extract industries is now. For most plant extract

commodities, a decade will be required to conduct

further research and establish a stable position in

domestic markets. Thus, advance planning will be

necessary to bring import substituting industries

up to scale before U.S. industry falls victim to the

next round of hyperinflation of raw materials

prices.

Another feature of global recession is the political-economic volatility of trade. Recession on a

global scale tends to increase nationalist sentiment,

especially in regimes that blame their economic

problems on “unfair” foreign competition (see, for

example, Business Week (4)). Economic nationalism

tends to involve protectionism vis-a-vis imports and

export subsidies to increase international sales of

domestic commodities. Economic nationalism thus

makes trade-related investments especially risky;

import substitution investments can be undermined

by other countries’ export subsidies, and where investments such as those in plant extracts industries

are premised on exports, export sales can be undermined by protectionist policies.

Another feature of the current socioeconomic

conjuncture is the increasing export dependency

of the United States with regard to its basic foodgrains, feedgrains, and oilseeds. Roughly 35 to 40

percent of the value of U.S. agricultural production

is exported, making farmers’ incomes highly dependent upon maintenance or expansion of export

markets. Moreover, virtually all forecasts of agricultural markets over the next several decades indicate that a growing proportion of farmers’ gross

receipts will be from exports (8,12,17). However,

the current global recession, combined with the

5-year legacy of the executive branch suspending

certain international grain sales as a foreign policy

lever, has undermined agricultural export earnings

and exacerbated the farm crisis (16). Thus, counterbalancing an otherwise gloomy situation for plant

extracts industries deriving from international economic stagnation, the disproportionate burden of

economic stagnation borne by farmers will no

doubt make agricultural diversification look increasingly attractive for both producers and Federal officials. Diversification of markets can benefit

producers in obvious ways, while the Federal Government should welcome strategies that can shrink

costly Federal commodity programs.

Most plant extract commodities discussed in the

10 workshop papers will require considerable additional R&D investment for commercial scale-up,

However, current conditions for expansion of R&D

in the public sector are unfavorable. Over the past

several years there has been stagnant or declining

support by the Federal Government for nonmilitary

R&D, including agricultural research. * Moreover,

Federal fiscal austerity and accompanying cutbacks

in Federal support of applied research have a questionable justification-that the private sector should

shoulder a greater burden for applied research,

while publicly funded research should be confined

largely to basic research. To be sure, science policy

should not encourage duplication of effort by underwriting public research that focuses on problems more efficiently explored by the private-sector,

But such duplication of effort is not frequent or un-

● The Reagan administration recently appears to have reversed itself

with regard to the priority placed on basic science research funding. The

National Science Foundation apparently will receive a substantial funding increase in real terms (5). However, it would appear that Federal funding for applied research will experience stagnation in real terms over

the next several years.
Potentials for Extracting protein, Medicines, and Other Useful Chemicals From Plants: Some Sociological Observations . 223

warranted, and the withdrawal of public support

from applied research relating to industries, such

as plant extracts, could be quite crippling. For example, front-end research required to stimulate

plant extracts industries is extremely varied and requires discrete sets of trained researchers and suitable research facilities. A large share of these research tasks could be accomplished efficiently

through grants to established research teams in universities or private research organizations. Wise

science policy must recognize that the now-popular

image of creating division of labor between university-based “basic” and private-sector-based “applied” research is suitable primarily for “high-tech”

sectors within large multinational firms with wellfunded, established research organizations. It

would be unrealistic to expect small- to mediumsized businesses to shoulder the burden of R&D in

numerous diverse areas ranging from agronomy,

plant breeding, physiology, microbiology, plant

pathology, entomology, engineering, bioassay, synthetic organic chemistry, market research, etc. The

current climate of retrenchment in public support

of applied research thus will be a substantial barrier to the development of the plant extracts industries. Congress should be urged to consider more

carefully the general long-term implications of

short-term savings in R&D spending and the specific problems such policies will cause for the expansion of the plant extracts sector.

A final aspect of the current socioeconomic milieu that will have crucial implications for industries seeking to extract useful chemicals from

plants is the emergence of genetic and cellular

manipulative technologies such as protoplasm fusion, cloning, tissue culture, recombinant DNA,

and immobilized enzymes. While these technologies will have positive long-term implications for

substituting natural substances for petrochemicals

and other nonrenewable resources (18), these technologies may at some prior point discourage investment and innovation because of the threat of rendering conventional plant extracts technologies obsolete. For example, recombinant DNA and industrial microbiology techniques may displace field

production of plants and chemical methods for extracting fractions of plant tissue. To help avoid this

conflict, it might be prudent for the Congress to encourage biotechnology research firms to take the

lead in selected areas of plant extracts technologies.

There are several biotechnology research firms

(e.g., the International Plant Research Institute,

Cetus, and Agrigenetics) that are oriented heavily

to research on agricultural crops and other higher

plants. Their agricultural capability and growing

expertise in industrial microbiological aspects of

industrial scale-up may make these firms highly

suited to the development of plant extracts technologies requiring agronomic and plant breeding research. At the same time, it should be recognized

that venture capital biotechnology firms will have

proprietary interests. Where it is undesirable for

research results to be proprietary property, R&D

subsidies should be directed to public research institutions such as State agricultural experiment stations or USDA’s Agricultural Research Service.

The Land Resource Base

Most potential plant extracts discussed in the 10

workshop reports involve cultivation and harvesting of higher plant species. In some cases (e.g., endod, neem), the species are perennials native to the

production region, and expanded use of these

plants would require little or no increased spatial

or ecological “demand” on the land resource base.

However, several plants—especially guayule,

crambe, jojoba, lesquerella, vernonia, kenaf, tobacco, milkweed, and conventional oilseed crops—if

used for plant extracts industries, would have

substantial implications for the quantity and quality

of U.S. land resources. This section thus will provide some observations on the degree to which the

U.S. land resource base would be adequate to support the cultivation of 60 or more million additional

acres of crops devoted to plant extracts.

The adequacy of the U.S. land resource base is

a very complex issue and has received increased

attention over the past decade (1,7,11,13,20). Land

resources will be more than sufficient to feed the

U.S. population and provide industrial raw materials (e.g., cotton, sugar, wool, wood) for the short

term. However, the adequacy of the land resource

base over the long term depends on certain unpredictable phenomena about which surprisingly little is known.

Probably the most unpredictable aspect of demand for land is the future level of export sales.

Over the past decade, roughly 35 to 40 percent of

U.S. agricultural production has been exported

and, as noted above, the consensus among econometric predictions of future trends is that it will increase perhaps to the point where over half of U.S.

agricultural production will be exported by 2010.

However, these predictions have been based on relatively favorable assumptions about global economic growth, and if the next few decades are characterized by continued economic stagnation, the level
224 . P/ants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

of export sales and hence demand on land resources may be considerably less than most analysts have anticipated. Further, levels of export

sales are not derived entirely from “natural” economic forces. Certainly, much of the rapid increase

in farm exports over the past 15 years has been accounted for by political considerations. Exports

have long been sought as a means to dispose of farm

surpluses and to increase farm income without Federal subsidies. The 1970’s and 1980’s reflect a continuation of this expectation which rarely has been

fully realized. In addition, farm exports have acquired added political importance due to their role

in reducing balance of payments deficits. The fact

that the next several decades promise little alteration in political conditions favoring the stimulation

of export sales suggests prudent caution: export

sales may not increase as rapidly and steadily as

was predicted a few years ago, but the most likely

prospect is to devote increasing numbers of acres

of farmland to producing feedgrains, woodgrains,

and oilseeds for export.

A second unpredictable factor is the nature and

pace of technological change in the direction of in

creased land productivity. It has been generally acknowledged that the 1970’s was a decade of relatively stagnant land productivity, and many observers felt that agricultural researchers had encountered limits to productivity growth through conventional plant and animal breeding (15). However, at

the same time that dire predictions were being

made about meager land productivity increases in

the U. S., biotechnological techniques (e.g., genetic:

engineering for increased photosynthetic efficiency) were emerging that promised continued advances in per acre yields. Unfortunately, these new

technologies remain at such an early stage of development that it is difficult to speculate on the timing or consequences of their commercial deployment, and hence on their impacts on the land resource base.

Complicating international trade and technological uncertainties about demand for land resources

are disagreements over recent historical trends that

have affected the quantity and quality of land resources available for production of agricultural and

industrial raw materials. The first is the extent and

significance of the loss of agricultural land to urban development, water impoundments, highways,

airports, etc. While it has been assumed that irreversible conversion of farm land to other uses has

been significant (approximately 3 to 5 million acres

per year), recent evidence questions the accuracy

of these data and argues that this loss of agricultural land will be relatively trivial in the next several

decades (20). The second area of disagreement has

focused around soil erosion and related forms of

land degradation. While it is generally recognized

that soil erosion in many areas of the country remains unacceptably high, there is considerable disagreement over the degree to which land degradation will limit agricultural productivity in the future

(7,8,17,19,23,24,26).*

One final complicating factor in anticipating the

availability of land for plant extracts production is

the extent to which land will be used to produce

biomass energy. Late-1970’s enthusiasm about

using agricultural biomass for energy has, of

course, subsided now that the real price of energy

has been reduced to levels approaching pre-Arab

oil embargo figures. Yet, petroleum markets may

tighten again and resultant increases in the real

price of energy may cause a significant allocation

of agricultural land to energy production.

Of the 10 reports, that by Tankersley and Wheaton pays the greatest attention to land resource questions, primarily because the plant extracts potentials discussed in this paper have the greatest implications for pressing against the limits of the U.S.

land resource base. Tankersley and Wheaton point

out that “production of one-third to one-half of the

industrial materials (presently) purchased abroad

would demand about 60 million acres of cropland.”

While this increased demand on the land resource

base would entail roughly a 20 percent expansion

of land in crop production over the 1979 figure of

348 million acres, the authors are relatively unconcerned about plant extracts industries creating

undue pressure on land resources. Two rationales

undergird this argument. First, Tankersley and

Wheaton cite data that there are “36 million acres

of pasture and other land in farms that can be easily converted to the production of crops with little

costs” and that the U.S. “has about 96 million acres

of land that can be converted to crop production

with more difficulty and cost than the 36 million

acres cited above. ” Given that “the Nation’s total

cropland base . . . is 540 million acres” and “projections made by the Department of Agriculture

. [that] about 462 million acres of cropland will

be needed in the year 2030 to meet domestic and

foreign trade demands for food and fiber,” 78 million acres of cropland would remain to devote to

plant extracts industries and other land uses. Be-

● See alm Impacts of Technology on U.S. Cropland and Rangeland Productivi~ (Washington, D. C.: U.S. Congress, OffIce of Technology Assessment, OTA-F-166, August 1982).
Potentials for Extracting Protein, Medicines, and Other Useful Chemicals From Plants: Some Sociological Observations . 225

cause these 78 million “slack” areas are in excess

of the 60 million acre estimate of the land required

to substitute for one-third to one-half of industrial

materials purchased abroad, the authors see little

problem with regard to the adequacy of the land

resource base. Second, the authors see clear public

benefits associated with pressing up to the limits

of the agricultural land base; “at that rate of utilization, there should be no need for farm commodity

support or subsidization programs for food and fiber.”

Several points can be raised about the inferences

the authors have drawn from these data. First, I

would urge a more cautious point of view with regard to the ease of conversion of land now used for

pasture and other purposes into cropland. Most of

this land is withheld from cropping for the simple

reason that it is too steeply sloped, too poorly

drained, etc. to justify cultivation in an intensive

cropping regime. The authors quite correctly imply

that noncropland “in farms” is easier to convert to

cropping than land with no connection to operating

farms, Nevertheless, there is by no means a consensus among researchers about the ease or cost

of converting such land to crops. *

Second, Tankersley and Wheaton’s arguments

about the “96 million acres of land . . . “ neglect

a crucial problem in reallocating this land to cropping. Because much of this land is owned by nonfarmers and is being “used” (e.g., as recreational

property), efforts to add this land to the effective

cropland base of the United States will encounter

two key problems. One will be transfer of control

or ownership, since it is likely that this land will

need to be leased or sold to farmers to be converted

to cropping. Second, given that the land is not idle

in the strict sense—i.e., the land is being enjoyed

or otherwise used for some purpose that contributes to human satisfaction—returns from cropping

the land must be fairly substantial to induce a shift

from its current pattern of use.

Third, I have reservations about Tankersley and

Wheaton’s ideas on “utilization rate.” The authors

operationalize this rate as the number of acres of

land in crops divided by the number of acres in the

potential cropland base (times 100). The implication is that the higher the utilization rate, the more

efficiently cropland resources are being used. A

utilization rate approaching 100 percent should not

*Tankersley and Wheaton’s optimistic assessments of the amount of

land that can be converted into plant extracts production (and of the

speed of this conversion) can be contrasted with the much more

pessimistic results reported by Doering (9,10) with regard to converting

noncropland for biomass energy production.

be regarded as unambiguously desirable. As noted

earlier, the extent of demands on the U.S. cropland

base are difficult to predict three or four decades

into the future. Therefore, a moderate “utilization

rate” would seem to be more prudent than a rate

approaching 100 percent. Intensive cultivation of

marginal lands, even under the best circumstances,

threatens to degrade the quality of this land and

other resources (e.g., soil erosion and fertilizer

runoff leading to sedimentation and eutrophication

of lakes and streams). Moreover, a moderate utilization rate enables the society to have a land reserve

which can be drawn upon in the event of unforeseeable circumstances. I suggest that policy makers

be cautious in pressing the use of fragile lands to

their limits and thus reducing land use options in

the future.

In a certain sense, posing the issue as we have—

asking whether the sum total of demands for agricultural land will exceed the supply of land—is

unrealistic. The use of land will be determined in

great part by market forces. Given this reality, it will

be important, however, for policymakers to ask:

which uses of land are essential or socially desirable

and should be encouraged, and which are less essential and do not deserve public subsidies? My

own view is that the use of land for both plant extracts feedstocks and low-intensity reserves of lowto moderate-productivity land serve the societal

good, albeit in very different ways. Most importantly, as demands on the U.S. land resource base increase over the next decades, policy makers, essentially for the first time in history, will have to grapple with the costs and benefits of particular land

uses and make explicit decisions to encourage or

discourage particular uses of land.

Research and Development Aspects

of the Plant Extracts Industries

The potential commercial crops discussed in the

workshop vary greatly according to “front-end”

R&D requirements, Even the plant sectors requiring only modest amounts of R&D before widespread commercialization becomes possible need

a suitable R&D system that can produce continued

refinements in on-farm production and nonfarm industrial techniques. Thus, much of the future of the

plant extracts sectors will depend upon establishment of appropriate R&D systems that can facilitate

breakthroughs and continued fine-tuning.

It is important to emphasize the particularly complex nature of plant extract research and development requirements. Most plant extract commodi-
226 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop proceedings

ties require a long chain of research tasks. This is,

of course, most true for pharmaceutical commodities and somewhat less so for biocidal materials,

given the necessarily long and careful procedures

required for licensing of substances that might have

deleterious impacts on humans or other life forms.

Also, most of the plant extract commodities that involve agricultural production face R&D requirements spanning a variety of scientific disciplines.

Perhaps the most difficult problem is that these

agriculturally related commodities require agronomic and related research—the bulk of expertise

for which lies in public, land-grant institutions—

and industrial biochemistry and engineering research—the bulk of which is now privately funded

and entered into on a proprietary basis. Moreover,

the situation becomes even more complex if byproduct use is required to begin commercial scaleup, Coordination and control will be potentially

crippling problems in linking research advances

made in what previously have been relatively distinct segments of the U.S. R&D system.

Despite the fact that virtually every plant extract

commodity discussed would require a combination

of public and private research, none of the papers,

with the partial exception of Farnsworth and Loub,

make explicit recommendations about how public

and private funds and institutions should be combined to advance the plant extract industries. Also,

I am struck by the large amount of basic “agronomic” (including parallel disciplinary work in plant

breeding, plant pathology, entomology, and soil science) research that will be required to realize the

full potential of the agriculturally related plant extracts such as milkweed, guayule, jojoba, crambe,

etc. Related data on potential ecological impacts of

commercial scale production of these commodities

are also generally lacking in the papers (and in the

scientific literature).

The crucial problem for the plant extract industries will be how to leverage public and private

funds for R&D in ways that private companies will

not be inappropriately subsidized or discouraged

from entering the industry. It was noted above that

the public nonmilitary R&D sector (especially for

publicly funded applied research) faces stagnating

or declining budgets (in real terms). Thus, adding

significant research responsibilities for a number

of nonconventional crops would severely strain the

resources of the publicly funded State agricultural

experiment station (SAES) and ARS systems. Moreover, the SAES and ARS systems are implicated in

what may prove to be severe crises of public confidence; many agricultural research administrators

and agricultural experts outside of the system are

questioning whether this system is yielding high

quality, “cutting-edge” research (21). It is likely that

traditional formula funding appropriations for the

SAES will stagnate in real terms over the next several decades and that any real increases in agricultural research funds will come in the form of “competitive grants” (which in theory would be available to nonland-grant as well as land-grant researchers). Thus, Congress should strongly consider making plant extracts research a high priority item and make funding available through a competitive grants program administered through

USDA. This is not to argue that individual landgrant SAES should not pursue plant extracts-related research from their formula funds. Indeed,

such an allocation of funds would be highly desirable. However, it should be recognized that the

pressure on the use of these funds from traditional

commodity and other clientele groups of the SAES

will be increasingly intense as formula funding

levels stagnate, and plant extracts “interests,” being relatively new and not so entrenched as traditional commodity groups, cannot hope to fare well

in this intensified competition for scarce research

resources.

Private research funding problems are of a quite

different nature. The bulk of privately funded research is conducted in two major sectors: “venture

capital” (or other small) firms and large multiproduct translational companies. The venture capital

sector has several advantages and disadvantages as

a locus for plant extract research. On one hand,

venture capital firms tend to be more risk-taking

in their approach and typically are able to attract

high-quality scientific talent because their working

conditions by comparison with large corporations

are more similar to those of a university. At the

same time, venture capital firm research tends to

be volatile, as it depends on the continued faith of

venture capitalist investors; redundant, as several

venture capital firms pursue similar research topics; and short term, since venture capital firms must

“strike it rich” with immediate discoveries in order

to survive beyond the initial period of venture capital funding. Moreover, most venture capital firms

tend to have a “high-tech” bias—i.e., they are

typically oriented toward highly advanced technologies which lead to valuable patents. Finally, most

venture capital firms are too small to be effective

in industrial scale-up.

The R&D systems of large transnationals generally tend to be more stable than those of venture

capital firms because long-term funding is secure.
Potentials for Extracting Protein, Medicines, and Other Useful Chemicals From Plants: Some Sociological Observations ● 227

However, large firms’ R&D tend to be relatively

conservative and focused on differentiation of current product lines. Innovative research in areas

such as plant extracts frequently promises to

threaten existing product lines. For example, a

large agrochemical firm maybe reluctant to explore

plant-derived biocides, since these biocides might

cut into the sales of existing product lines and

create research information that could lead competitors to provide substitutes for their products.

Evidence presented in several of the workshop

papers and other literature suggests that private

sector plant extracts research would be more likely to occur in the small or venture capital firm sector than in the translational sector. The following

comments, therefore, will focus on ways in which

research results generated in public SAES/ARS and

private venture capital institutions can be coordinated to develop plant extracts industries. One of

the limitations in examining this issue is that the

workshop papers contain little information on

which types of research will be privately profitable

(and hence attractive for the private Sector) and

which will not (and hence needed to be conducted

by the public sector or be publicly funded and contracted out to private firms). Thus, were Congress

to be asked to enact legislation encouraging plant

extracts industries, the aspects of plant extracts

R&D that will be profitable to private firms to conduct and those that will require public subsidies

should be determined.

As indicated earlier, publicly funded “front-end”

research to stimulate private interest in the potentials of plant extract production probably will be

needed, Some of this research may be expected to

come from existing allocations within the SAES/

ARS systems, but Congress may also need to consider a competitive grants program in the plant extracts area to allocate adequate research resources

to these problems.

The private research organizations should not be

solely responsible for research which is perceived

to be privately profitable; the plant extracts industry

as a whole may suffer if crucial patents become

dominated by single firms. Public institutions

should not avoid sponsoring research in areas that

are attractive to private firms, since retaining certain crucial discoveries in the public domain may

be essential to allow more than one firm to enter

an industry. Nevertheless, it should be recognized

that the bulk of the “industrial-level” research in

plant extracts (e.g., fractionation processes, byproduct utilization) can and should be confined primarily to the private sector.

Plant extracts R&D will by necessity confront two

issues that have assumed general importance in

U.S. nonmilitary R&D. The first is the relationship

between public and private research. During the

past several years the U.S. R&D system has been

in flux over the “proper” roles for public and

private research. The mix of public and private research is now a major issue on many campuses (6)

and in State and Federal Governments. It is recognized that public research should be coordinated

more closely with the technical needs of industry,

especially given the intense international technological competition that emerged during the late

1970’s and early 1980’s, However, there remains a

great deal of uneasiness about how corporate influence on academic research priorities and procedures (especially control over the content of research and over patenting and licensing) will reduce academic freedom, stifle scholarly communication, and deflect research attention from projects

that are of little interest to private firms but might

be important to long-term public interest. The second current issue within which plant extracts will

be implicated is the desirability of patenting life

forms (and the corollary provisions of varietal protection offered by the Plant Variety Protection Act

of 1970). On one hand, protection of proprietary interests in developing new varieties and life forms

will encourage private sector research in these

areas and reduce the level of public funding required to stimulate the agricultural and chemical-pharmaceutical industries. On the other hand,

protection of new varieties and novel life forms

raises certain ethical questions and may serve to

deter public R&D in this area and keep useful plant

varieties out of the public sector, It is useful to keep

these issues in mind when formulating policy to encourage the plant extracts industries and to anticipate possible problems before they develop,

The Organization of Primary

Production

This section will comment in general fashion on

the papers, especially those by Telek, Wildman, and

Tankersley and Wheaton, which discuss plant extracts processes requiring significant field crop production. The main concern will be how the primary

production (or “farming”) segment of these industries will be organized and the effects of these organizational structures.

The papers under review give virtually no information on how the primary production segment of
228 ● P/ants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

the plant extracts industries will be organized. In

most cases this neglect is understandable; adequate

information is unavailable and/or outside the

author’s area of expertise. Nevertheless, in exploring the potential of developing particular plant extracts, greater attention should be given to anticipating the socioeconomic structures and consequences that would result in the primary production area.

One crucial aspect of the organizational structure

of the plant extract industries will be land availability. Land assembly arrangements will differ according to whether the land involved is owned by or

leased to farmers and is cultivated. For lands

owned or otherwise operated by farmers and currently under production, the crucial issue is: How

will operators of these lands be induced to shift

their uses of land? For land not under production,

especially land not owned or controlled by farmers,

the most important question concerns how these

lands can enter agricultural production and, if

necessary, undergo a transfer of ownership and

control into the hands of farmers.

Inducing shifts of land from one agricultural use

to another is basically a straightforward economic

question. Commodity prices will have to be competitive with those of other crops, and mechanisms

will be required to reduce the producer’s risk. Newly developed crops can be competitive in the short

run with traditional crops if an extract or product

from the new crop is introduced as a “specialty”

item. This high-value extract becomes a vector for

greater long-term development of the crop for that

and other products. By capitalizing on a novel or

specialty item, the crop can be grown in restricted

quantities for favorable prices, ensuring adequate

and predictable returns for farmers and providing

them with experience in growing the commodity

and the opportunity to iron out production problems (e.g., tillage practices, pest control, variety

selection). Initiating production of a new agricultural commodity in this way will provide the time

necessary to complete further agronomic research

and research in industrial engineering or byproduct use that will be critical to the long-term development of the industry. Nevertheless, incentives may

be required to encourage farmers to shift their agricultural land from one crop to another, and contracting for guaranteed commodity prices or guaranteed returns may be an essential incentive necessary to effect this crop shift.

One question that may warrant attention in future

technology assessments of plant extracts is the

possible impacts of growing new agricultural crops

on the production of other commodities such as

wheat or sorghum and on the communities in

which these new crops are grown. Generally, I

suspect that the impacts on production levels of

conventional crops would not be substantial or undesirable. Most field crop production in the United

States has a large geographical range so that regionally confined shifts in cropping patterns would not

greatly reduce the supply of other commodities.

Perhaps more crucial might be “boomtown” effects

of rapid growth and possible subsequent decline of

the on-farm and off-farm segments of a plant extract process. Sociological attention recently has

been focused on dislocating community-level impacts of boomtowns, both on the “upcycle” and on

the “downcycle.” In the upcycle, rapid increases

in employment and population stretch public services to their breaking point, result in influxes of

“outsiders,” place pressure on and result in inflation in the value of housing stock, economically

marginalize segments of long-term residents (especially the elderly), etc. (25). The dislocating effects

of the (“ghost town”) downcycle are obvious—deflation of asset values, loss of tax base, high unemployment, and so on. Thus, attention should be

given to situations in which the development of

plant extracts industries, particularly in what are

now sparsely populated rural areas, might lead to

a boomtown syndrome.

Earlier I alluded to several problems resulting

from shifts of land into plant extracts agriculture.

Unfortunately, our research and data base on land

ownership in the United States are so inadequate

that we lack sufficient profiles on the persons who

own farmland that is not in farms and on the motivations for these ownership patterns. The scanty

literature on this topic indicates that most of these

lands are owned for esthetic and land speculation

reasons and would not be shifted into agricultural

production easily. One mechanism for shifting public lands, especially in the semiarid West, would be

leasing these public lands for an indefinite period

or perhaps selling them to farmers after a period

of time. In sum, existing knowledge on the possible mechanisms for assembling land not currently

in farms is highly inadequate for policy purposes.

Identifying underused publicly owned lands in certain parts of the country for plant extracts purposes

may be the most satisfactory short-term solution to

the land assembly problem.

In addition to the neglect of land assembly issues,

the workshop papers ignored the question of

whether expanded agricultural production of plant

extracts feedstocks will reinforce or undermine
Potentials for extracting Protein, Medicines, and Other Useful Chemicals From Plants: Some Sociological Observations . 229

family forms of agricultural production, Several key

types of data will be required to address this issue,

First, and most important, we need information on

expected economies of scale in production, since

one may assume that commodities for which there

are substantial economies of scale will tend to be

produced under large-scale “corporate” or “industrial” conditions. Second, information is needed on

the amounts and types of labor required for production; for example, commodities that require

large amounts of unskilled, cheap labor can be expected to be produced under nonfamily arrangements. Third, data are required on the capital-intensity of production (since highly capital-intensive

production techniques tend to be biased against

family farming units).

It can be argued that there will be social (especially community-level) benefits to the degree to which

agricultural production can be undertaken by family (as opposed to industrial scale) producers (2,22).

This is the case where the agricultural production

process can be conducted without using a low-wage

labor force, since a poorly remunerated labor force

tends to have low purchasing power vis-a-vis local

businesses. Where possible, the establishment of

plant extract-related agricultural production should

encourage family forms of production, and R&D

should be oriented toward minimizing the barriers

(such as high capital-intensity) to family farming

units entering this area of production.

Organization of Nonfarm

Plant Extracts Industries

For plant extracts industries to reach their full

potential, R&D and pilot operations will have to be

scaled up into commercial sized facilities. Scale-up

involves both technical engineering and socioeconomic aspects. Chief among the socioeconomic aspects are the organizational routes to increased

scale and the corollary processes of capital assembly. The scale-up process typically involves one of

three major routes. The first route is for a small firm

to pioneer in a pilot project, nurture the new technology, prosper, and acquire the capital necessary

to become a large firm. The second route is for a

small pioneering firm to sell out to a larger firm

because of asset appreciation or lack of capital necessary to achieve the next level or stage of scaleup. The third route is for the technology to be developed within a large firm and for the large firm

to undertake the investments involved in commercial scale up. The plant extracts industries no doubt

will exhibit a variety of paths to commercial scaleup, probably involving all three routes.

The most crucial problem for development of the

plant extracts industries is not the route followed

for commercial scale, but whether the process will

become stalled before the commercial scale-up occurs. As suggested earlier, smaller firms can be expected to be most innovative with regard to industrial processes such as plant extracts. However,

these firms tend to have fragile financial bases and

may lack the engineering expertise necessary to develop a plant extracts process beyond pilot scale,

Larger firms tend to have greater industrial engineering expertise but may not be attracted to industrial production activities that lack secure patent protection or compete with existing product

lines.

One of the major types of data necessary to judge

the future of plant extracts industries—the likely

degree of economies of scale and lumpiness of investments—generally was absent in the workshop

papers under review. These data would help policymakers anticipate the likely route to commercial

scale-up and the problems that might emerge during the process of industrial maturation.

A final comment I would like to make about the

organization of the nonfarm plant extracts industry

is to provide a general observation about patterns

of industrial innovation in other advanced industrial societies, The problems involved in nurturing

new industries are by no means unique to the

United States. However, it can be observed that the

United States has become one of the most traditional societies in recent years in reorganizing industry

and fostering new industries. Virtually all other advanced industrial societies are experimenting with

State-private corporations, or other “mixed” enterprises or forms of State-corporate cooperation, as

means to achieve industrial policy goals. For example, the Japanese, through their Ministry of International Trade and Industry, are carefully aiming

public R&D funds at selected industries for the explicit purpose of stimulating industrial innovation

and gaining national advantage over other international trade rivals (especially the United States).

More overt patterns of public-private cooperation

and State-private industrial partnerships have occurred in France (3). Even the United Kingdom,

under the conservative Thatcher regime, has initiated a number of State-owned corporations, in conjunction with private investments, in areas such as

biotechnology and biomedical technology. The

United States thus virtually stands alone in its

laissez-faire posture toward industrial reorganiza-
230 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

tion, and a growing number of analysts have suggested that this laissez-faire posture will result in

U.S. industry being outcompeted by foreign firms

which have the force of government finance, R&D,

and diplomacy at their disposal (14).

The implication with regard to plant extracts is

that Congress may need to consider what now are

regarded in the U.S. as novel forms of governmentindustry cooperation to nurture new industries in

the long-term public interest. Partially governmentowned firms need not, of course, remain publicly

owned for an extended period of time; these firms

may be sold to private investors after they become

sufficiently established and profitable and hence attractive to private firms. Nevertheless, U.S. policymakers may need to reexamine their orientation toward industrial policy and make judicious use of

public sector financial, R&D, and organizational

resources to nurture new industries such as plant

extracts.

Policy and Political Issues

This final section explores some selected public

policy and larger political issues that were raised

in several of the papers, especially that by Tankersley and Wheaton, and in the OTA workshop discussions. The first such issue involves the connection between an emerging plant extracts industry

and the level of Federal commodity programs for

basic grains and other agricultural commodities.

Agricultural diversification implied by a growing

plant extracts industry would expand markets and

reduce the need for increasingly expensive commodity programs. To the degree that U.S. agriculture (especially in the Great Plains and Midwest)

becomes increasingly specialized in the production

of a handful of feedgrains, foodgrains, and oilseeds—much of which is destined for export—the

agricultural sector will face price and income instability and may need commodity price supports

and deficiency payments. Agricultural diversification will reduce the supply of these grains and oilseeds that have been chronically overproduced and

reduce government expenditures for mitigating

economic dislocation in the farm sector.

At the same time that one might argue that agricultural diversification will reduce commodity program expenditures, one should urge caution in

drastically modifying these programs. Reduction of

the scope of these programs will be a relatively long

process. Commodity groups that are advantaged by

Federal commodity programs can be expected to

protect their prerogatives for an extended period

of time. One should be aware of the extended time

frame over which agricultural diversification will

occur and of the underlying reasons why these

commodity programs were enacted and why they

will be needed some time into the future.

The role of commodity programs has been cast

into sharp relief during the present farm recession.

Without government intervention, the agricultural

recession would have resulted in more dramatic

dislocations among farmers. For example, in most

areas of the country farmland prices have already

declined by about 15 percent. As asset values decrease, farmers’ collateral for loans shrinks and

bankers may be forced to foreclose on farmers for

whom current losses overwhelm equity in farm assets. Federal commodity programs are thus a necessary evil to prevent a severe depreciation in the

value of farm assets and to prevent massive farm

foreclosures.

In summary, there are several interrelated arguments about farm commodity programs. First, a

time of farm recession is not propitious for the initiation of public policies to reduce commodity program payments. Second, there probably will be

some continuing need for price and/or income sup

ports for basic foodgrains, feedgrains, and other

commodities which are characterized by low price

and income elasticities of demand and, hence, by

price and income volatility for farmers. Third, it

would be politically unrealistic to suggest that farm

commodity programs can be dramatically curtailed,

especially in the very near future, over the objection of powerful commodity organizations. Fourth,

agricultural diversification, such as through encouragement of plant extracts industries, will, in

the long run, reduce the need for and expenditures

on traditional agricultural commodity programs.

A second policy/political issue of concern to plant

extracts is a short cautionary note with regard to

the geopolitical implications of nurturing these industries. It is becoming increasingly apparent that

foreign trade issues are not matters of mere abstract

economic forces. Foreign trade is becoming increasingly central to the economic health of all advanced industrial societies which must be increasingly concerned about the international competitiveness of their industries and about their foreign

trade balances. Import substitution is, in a sense,

a form of import protectionism—albeit a much

more benign form than increased import duties or

import quotas—and Federal policy makers will need

to be cautious about the geopolitical problems that

could result from government support of import

substitution efforts.
Potentials for extracting Protein, Medicines, and Other Useful Chemicals From Plants: Some Sociological Observations ● 231

A final policy issue is that Congress should recognize that some plant extracts processes have

more potential than others and that public support

should be given selectively and carefully. To illustrate, I would like to use the example of protein

from tobacco (Wildman). I do not wish to imply that

this process is without merit or undeserving of public support; however, I feel there are certain key

problems with the development of such an industry

that were not adequately addressed in the paper by

Wildman. First, as brought out in the OTA discussion, there are public acceptability problems associated with food uses of tobacco. Second, and perhaps more important, there are market problems

with any type of vegetable protein for human consumption, as has been made dramatically apparent

during the past 10 years of initiatives to market soy

protein as a substitute for meat. Soy protein had

great promise; nutritionally, the product was quite

adequate, and soy protein promised to widen greatly access to high-quality protein because it was

cheaper than meat. However, in a global marketing

sense, soy protein essentially failed for one simple

reason: There are two types of people in the

world—those who can afford any type of protein

and those who cannot—and those persons who can

afford protein greatly prefer to buy it in the form

of meat. Thus, the great promise of protein for

humans from tobacco may take a long time to be

realized. LPC protein for animal feed may thus have

greater short- to medium-term potential than human food protein from tobacco. This example illustrates that the actual market potential of a plant

extracts commodity may be less than it appears on

the surface. Policy makers will have to acquire more

detailed social science and marketing information

on many plant extracts commodities to determine

more accurately their market potential.

1.

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J. Bryan,” Forbes 109-114, Aug. 30, 1982.

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R, B. Talbot (eds.) (New York: The Academy of Political Science, 1982), pp. 99-111.

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and Animals (Washington, D. C.: U.S. Government

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232 . Plants: The Potentials for Extracting protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Change,” Structure of Agriculture and Information

Needs Regarding Small Farms, L. Tweeten, et al.

(eds.) (Washington, D. C.: National Rural Center,

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American Agriculture.” The Future of American

Agriculture as a Strategic Resource, S. S. Batie and

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Chevy Chase, Md., December 1982.
PLANTS: THE POTENTIALS FOR EXTRACTlNG PROTEIN,

MEDIClNES, AND OTHER USEFUL CHEMICALS

(A Review of the OTA Workshop Papers)

Cornelia Butler Flora

Department of Sociology, Anthropology, and Social Work

Kansas State University

An Altenate Use for Tobacco

Agriculture: Proteins for food Plus a

Safer Smoking Material

by Samuel Wildman

The technology for extracting leaf protein has

more important societal implications than the use

of tobacco for protein. There are many reasons why

tobacco leaf protein would be unacceptable in

scarce resource situations such as in developing

areas. The enormous amount of nitrogen fertilizer

needed to produce tobacco protein is expensive and

would be prohibitive in developing countries where

imports of chemical fertilizers require the use of

foreign exchange. A cost comparison of producing

regular tobacco and producing tobacco for leaf protein on a per-acre basis is needed to judge the potential costs to the farmer. Because leaf attractiveness

is not so important for tobacco grown for protein

extraction, pesticide inputs would be less than in

conventional production. The higher input costs accrued through four annual cuttings, each requiring

fertilization, must be weighed against a higher

value product. These tradeoffs must be examined

in greater depth.

This technology is biased toward resource advantaged U.S. farmers because this kind of tobacco production is capital intensive in its use of nitrogen

fertilizer and harvesting machinery. Resource disadvantaged farmers, particularly the small allotment holders in the rural South, would become

even less competitive with the larger farmers,

ultimately becoming more reliant on subsidies and

less able to survive in a free market situation.

Although the allotment system for tobacco may be

a disadvantage to the ultimate rationality of farming in the South, by maintaining small farmers on

the land, it has had important social benefits, A

move to tobacco leaf protein may counteract that

social welfare by shifting resources from less advantaged to more advantaged farmers.

The sociological problem of integrating an innovative structure of production into an ongoing

technological system seems to be the biggest constraint faced by the tobacco protein project. The

unique mechanism of physically and chemically

fractionating the leaf and extracting Fraction 1 protein appears to be an important breakthrough that

could be used for a variety of plants besides tobacco. Other plants may not have the established allotment structure and the established growers network of tobacco, but their products might be more

readily accepted by the public. A nitrogen-fixing

plant seems more appropriate because it would require lower fertilizer inputs.

Once the leaf protein is produced, there are marketing and market penetration problems that are

difficult for small entrepreneurs to overcome. The

medical market for leaf protein seems logical, but

it is small, not particularly lucrative, and unlikely

to support the large investment needed for protein

extraction. The other products that the leaf protein

might replace, such as egg albumin, are not in short

supply. For example, the poultry industry is well

developed. There would have to be a large price incentive for industries to seek a new product as a

substitute to egg albumin in food processing. A

substitution would require some production shifts

in tooling or processing, and food industries seem

particularly unwilling to make such shifts.

One argument of the large food manufacturers

against the new product is that leaf protein from

tobacco would prompt consumer groups to launch

antinicotine campaigns, Possible problems arising

with labeling—consumer acceptance of a product

labeled as containing tobacco protein—may compound the difficulties facing tobacco leaf protein,

An alternative crop for this technology was not

explored by Leaf Proteins, Inc. Soybeans or peanut

leaves might be good substitutes in the South. Because they are nitrogen fixers, they require less fertilizer, therefore reducing crop costs and possibly

increasing the profit per hectare. Initial profitability

for the grower and producer of a vegetable protein

product would have to be highly subsidized by State

and Federal Governments. The commodity focus

of U.S. agricultural development has limited the

development of new crops, and subsidies to tobacco allotments inhibits the potential competitiveness

of alternative crops.

The potential for local production must be determined when considering leaf protein as a dietary

supplement for developing countries. As most developing countries have limited foreign exchange

and are in a high debt squeeze, most protein for

human consumption must be processed locally.

The protein extraction process might be appropri233
234 . Plants: The Potent/a/s for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

ate in developing countries where the State sector

is active and will subsidize some of the initial startup costs. In these countries, it is unlikely that tobacco would be the crop chosen for leaf protein extraction, however, except perhaps in the People’s Republic of China, which already grows a great deal

of tobacco.

In countries producing sugar, which has low current and expected world market prices, the sugarcane grinders and centrifuges might be modified

for leaf protein extraction. However, the cost of

machinery conversion probably would have to be

borne by the State, and establishing distribution

channels at first would have to be underwritten

through grants and soft loans. It is doubtful that the

protein could ever be self-supporting in poverty-

-stricken markets; it would have to be instigated as

a social welfare measure.

The dehydrated alfalfa process provides an example of leaf protein extraction in the United

States. It would be instructive to look at the problems of Pro-Xan processing and marketing.

If leaf protein were to be extracted from tobacco

or other crops, plant breeders would have to reorient their breeding thrust. For example, if one were

to use soybeans, one would stop breeding primarily

for bean quality and also emphasize increased leaf

mass and protein content. Bringing about a shift

in breeder ideology might be a problem. Reputations in tobacco breeding sometimes have been

made on a leaf appearance rather than foliage

density.

The use of this new product would have to be

linked closely to its manufacture. At first the process might be vertically integrated from contract

growing to manufacturing, particularly if a new variety of tobacco or soybean were used. Once the

new crop is established, contract growing probably

would cease because it would be more profitable

for the food manufacturer to buy on the open market.

In Third World countries, the use of tobacco instead of soybeans or another nitrogen-fixing food

crop as a source of protein would have to be considered carefully. Alternatives to tobacco should be

sought. Efforts are in progress to breed a tropical

soybean that could be grown in areas where tobacco now is grown. The advantages of extracting protein from soybeans or peanuts instead of tobacco

is that soybean and peanuts are nitrogen fixers, and

the beans can be used directly as food or as a source

of marketable oils. One criterion for choosing

plants for protein extraction is that the plant or

combination of plants provide leaves for a good

portion of the year to avoid the costs of supporting

idle machinery and the negative effects of a seasonal labor force.

For leaf protein to be a solution to Third World

food problems, it would have to be produced locally

at low cost. Available machinery should be adapted

to avoid debts incurred for importing processing

plants. Protein production would not generate foreign exchange because money from local sales cannot be used to repay most loans, and leaf protein

produced in Third World countries probably would

not be sold on an international market.

Loaf Protein Extraction Fro m

Tropical Plants

by Lehel Telek

Telek’s discussion is aimed primarily at Third

World countries. The process he reports is considerably simpler and cheaper than that suggested by

Wildman. Telek’s system of extraction deals with

protein for animal fodder instead of the higher

priced human food market. This process might be

adapted to cooperatives, organized communities,

or sugar refineries which, as protein extraction factories, could use their equipment and labor more

economically year round.

This method of leaf protein processing is best

suited for a relatively large, integrated operation of

animals and plants. In the Third World, the ideal

10-cow/hundred-hog production unit is that of a

wealthy farmer. Small peasant farmers have too few

animals to apply the process effectively. Further,

in most developing countries, few people eat animal protein, so the emphasis on fodder for larger

animal herds will have little impact on the poor,

landless worker or semiproletarianized peasant in

most of the Third World. The process seems best

adapted to centrally planned economies or cooperative production units.

Using a tractor as an energy source greatly limits

the type of farmers for which such technology

might be attractive. The price of tractors leaves few

peasant farmers the option of this technology. In

the Third World, as in the United States, large scale

animal production now tends to be based on purchasing feed inputs rather than producing them on

the farm.

Leaf protein extraction might encourage more integrated farming enterprises, which raise livestock

and produce livestock feed on the same farm. This

would require a high level of planning and coordination, and probably is most appropriate for
P/ants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals ● 235

either the public sector or highly capitalized,

management-intensive private entities, such as

companies producing beef for export, However,

these entities would be more likely to supplement

foreign exchange earnings and not directly increase

protein availability to the poor in these countries.

The leaf protein technology described by Mr.

Telek seems more adaptable to U.S. farming situations, particularly farms where rising costs of inputs encourage self sufficiency. This technology

seems particularly appropriate for integrated dairy

operations that might be expanded to include some

hogs. The Cooperative Extension Service might

work with small implement dealers to introduce

this technology. The current crisis in farm incomes

encourages adoption of such low-cost machinery.

There is a danger in depending on protein supplement programs to solve the problems of malnutrition in developing countries. These programs,

particularly when imposed from the outside, often

serve to only temporarily deal with the symptoms

and not the causes of poverty. A community-controlled food supplement program that allows the

community to produce protein and distribute it

to children would be more successful in decreasing the number of malnourished children. More

data on cost of production are needed. In addition,

alternatives within the farming system should be

examined to determine which ways of producing

supplemental proteins—meat produced with LPC,

LPC for human consumption, or alternative sources

such as eggs from a community chicken-raising

project—are more in keeping with both nutritional

habits and production possibilities.

Molluscicidal and Other Economic

Potentials Of Endod

by Aklilu Lemma

The development of ended is a good example of

the potential of plants for community-controlled

solutions to community problems. Research on the

basic chemical properties of ended indicates its

potential to supply a low technology molluscicide

to control schistosomiasis. A similar communitybased program could be envisioned in countries

where malaria is a problem, since the ended berries have larvicidal properties effective against the

mosquito.

Ended seems to grow wild under a variety of conditions. Cultivating ended and introducing it into

new areas requires better knowledge of the plant’s

climate and soil requirements for optimal growth.

A community controlled program could be based

on intensive ended cultivation by the public or

private sector and treatment of infection sites with

ended applied by the community. In a communitybased project concerning public health problems,

the public sector would have to bear the start up

and research costs, and the community should be

able to keep the project going through its local tax

base and volunteer participation. The public sector would also have to be active in the educational

campaign to link the community’s actions to the

results obtained, thus encouraging long-term local

support and participation in the project. A monitoring system to gather statistics on the health impact

of such a program, such as decreased infant death

and disease incidence, would be beneficial. Unless

communities perceive schistosomiasis as a problem

and ended as a solution, continued community participation in possible future programs using ended

as a molluscocide is unlikely.

Because research and start-up costs for community-based disease control programs are substantial,

development assistance from more affluent countries may be needed. The crossover of benefits may

be substantial so that the donor countries benefit

at the same time as providing assistance. For example, mosquito control is a huge problem in many

areas of the United States where DDT is outlawed.

Ended could be an effective larvicide for mosquito

control in such areas as rice fields in the central

valleys of California where the mosquito is a consistent social irritant. Another possible application

for ended is control of crayfish which dig holes in

the dikes of rice paddies in California. Ended properly applied could reduce the costs of crayfish control and environmental problems of pesticide runoffs.

Ended research has progressed because of the

combined efforts of the private and public sectors.

Continued public sector support is necessary, The

participation of the United States in ended research

could both help alleviate Third World problems and

have payoffs at home by providing inexpensive, environmentally satisfactory biocides.

The Role of the Alkaloids of

Catharanthus Roseus . . . .

by Gordon Svoboda

Gordon Svoboda’s remarkable presentation on

the development of anti-cancer alkaloids from the

Madagascar periwinkle should be considered in a

larger context. A major pharmaceutical company,

in this case Eli Lily, had to have available capital
236 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

and be willing to risk it on such a “fishing expedition.”

While the initial discovery was made at a university at public expense, product development was

done by private enterprise. This link between basic

university research and applied industry research

seems to be an economically and socially beneficial

model that should be encouraged. This case study

appears to be unique, as no pharmaceutical company is doing botanic pharmaceutical research. It

is important to understand why this research has

been discontinued, especially since Dr. Svoboda’s

research apparently has been very profitable to Eli

Lilly.

Has research shifted from botanical to chemical

pharmaceuticals because chemical research can be

carried out more rapidly than botanical research?

Or, is industrial research funding being reduced in

general, and, if so, what public efforts can counteract that situation? One important thing to look at

is the potential linkage of university-based botanical

pharmaceutical research and industry application.

While the university should not be a tool of industry,

it is important that top researchers continue screening, the results from which could be useful to pharmaceutical company scientists for subsequent product development research.

Part of this process involves an availability to

both public and private sectors of past screening

results to indicate which botanical are worth product development efforts. The screening program

and linkage of this program to potential users require more study. The users, including private entities, must perceive that information on results of

screening is available, and preferably computer accessible.

The difficulty synthesizing these anticancer

drugs demonstrates that botanical and their biological sources have a continuing place in medicine. Despite the large number of leaves necessary

to produce a small amount of the anticancer drug,

a relatively small acreage is required for agricultural production. However, since growing probably

would be done under contract arrangements, with

production agreements between private farmers

and pharmaceutical companies, it might provide

price stability and a steady income for farmers who

otherwise might depend on a single commodity.

More information is needed on these kinds of

agreements and variations in contract farming

systems. When vertical integration is too intense

and the market is oversaturated, as in the broiler

industry, exploitation of the contract producer occurs, but when contracts are let simply to provide

the input necessary for an established industry, a

more equitable arrangement can be reached between the producer and the contractor.

Marine Plants: A Unique and

Unexplored Resource

by William Fenical

Marine sources of food, pharmaceuticals, pesticides, and industrial chemical feedstocks have great

commercial potential and may have much less negative impact than land-based botanical. Although

research seems to have been on the taxonomy of

marine organisms rather than their commercial potential, and only limited biochemical screening of

marine plants for possible commercial products has

been done, there are a number of interesting marine

plant constituents that might be valuable,

The one marine plant industry that has developed

in the United States, that of extracting agar, carageenan, and alginate from seaweeds, seems to be

highly mechanized. It is difficult to conceive that

this technology would be available to any but t he

largest multinational corporations. While certain

algae cultivation is labor intensive in Japan, it is

highly unlikely to be so in the United States. Thus,

economic benefits derived from marine research

would not necessarily accrue to small producers.

It appears that the public sector is not interested

in or prepared to undertake marine-based pharmaceutical research or screening in the near future,

but it is very important that these species be preserved until such time as they might prove useful.

Insomuch as pollution can radically alter the nature

of coastal habitats and their organisms, a critical

government role would be to ensure that t h e

oceans, particularly coastal areas, are kept as free

as possible from pollutants. The recent deregulation of industrial waste dumping into major oceans

may alter marine populations and ultimately decrease some sources of genetic variability. Perhaps

we may decide not to do the expensive research and

development necessary to develop marine products

now, but we should not limit our future chances

to do so by unregulated pollution of the oceans,

Insecticides, Insect Repellants ,

and Attractants From Arid/

Semiarid Land Plants

by Martin Jacobson

This paper points out that many useful insecticides are available from plants. One wonders why,
Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals Ž 237

if nicotine is an effective insecticide as indicated

by Jacobson, the work on tobacco does not consider

nicotine as an insecticide as well as a source of protein and cigarette fiber.

The work at USDA, Beltsville, on isolating and

identifying insect feeding deterrents in various

weeds and crop plants might provide alternative

crops for farmers if appropriate processing and

marketing structures were developed. Putting these

structures in place clearly would require government assistance, but ultimately might provide low

cost, more environmentally safe insecticides that

substantially could reduce the cost of crop production in the United States. These products also might

have an impact in Third World countries if they can

be produced with appropriate technology and little imported machinery. Some economies of scale

probably would give a slight advantage to larger

units of production over smaller peasant plots.

The work done by USDA at Beltsville in identifying potentially useful insecticidal plants must be

taken one step further-to production. Private and

public sector research to determine commerical

feasibility and establish marketing structures is the

next order of business.

Jacobson considers the neem tree to have the

most potential as a source of insecticides. More

agronomic information is needed to understand the

neem growth cycle and the scale on which neem

should be cultivated. The preliminary evidence suggests that neem could be a suitable cash crop for

small family farms and that processing need not be

done on a large scale. However, more work on scale

of cultivation and process and economic feasibility must be done and questions on labor and product distribution answered. For example, how much

local employment can neem seed processing generate? How much will this new industrial or semiindustrial development depend on established

transportation networks to distribute the insecticide products? How large would a neem plantation have to be in order to be commercially feasible? How does the harvest cycle relate to other

small farm labor demands?

The 5-year waiting time for the neem tree to bear

fruit necessitates that any project introducing

neem, especially projects in developing countries

with small farmers, must ensure that sources of

food and cash are available to the farm family for

the first 5 years. The problem of motivating farm

families to invest time, energy, and money in longterm payoff crops has to be examined when considering neem for commercial development in Third

World countries.

Processing and cultivation have to be linked to

markets from the beginning. The work already

under way on neem suggests that an appropriate

next step would be continued government support

linked with small scale private industry for processing and marketing the product,

In the United States, public lands or communally held lands, such as those of the American Indians, seem prime targets for planting neem trees.

However, labor requirements for harvest should be

examined seriously. How is harvesting done, how

many people must be involved, and how soon after

ripening must the seeds be harvested and processed? The frost susceptibility of the neem tree

might limit its use in Southwestern United States.

The possibilities for selective breeding or simply

selection for cold resistant species might be investigated. Land grant universities and small farmers

could be involved in this screening procedure.

Other important questions that must be examined

in regard to developing country production of the

plants mentioned by Jacobson are those of labor requirements and distribution of labor among different family members. Labor intensity at certain

times of the year may exclude small farmers, who

often are limited by labor availability, especially at

peak harvest times, from growing particular crops.

Crops that are labor intensive, but have labor requirements more evenly distributed throughout the

year, may be more appropriate for small farms. For

example, basil might be a good cash crop for farm

women. A marketing system would have to be developed and linked to industry, perhaps a small

scale community-based industry specializing in oil

from the basil plants.

Multiple product species, such as the mammyapple which yields an insecticide, wood, and fruit,

have potential for increasing local self-sufficiency

in developing countries. Systematic research on

processing requirements of such multipurpose

crops is needed. At this point, a good strategy might

be for communities to work on developing an industry where there would be local supply of the raw

inputs and local consumption of the outputs, It

would be necessary to link community and industrial capital interested in investing in up-scaling the

extraction procedure.

One of the important aspects in all of these crops

is that apparently a substantial amount of plant biomass is required to yield a commercially viable

amount of the product. This suggests that simple,

decentralized plants, using village labor and village

management which would increase the potential

for community control and regional self-suffi24-503 0 - 83 - 17
238 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

ciency, would be the best way to develop these

products. That would require working with local

communities at an early stage in the commercial

development of these crops.

Chemicals From Arid/Semiarid Land

hints: Whole Plant Use of Milkweeds

by Robert Adam

The use of arid and semiarid land plants as

sources of industrial chemical products is appealing. The Jacobson and Adams papers illustrate that

many of the common plants in arid and semiarid

areas have potential for product development. The

economic feasibility of cultivating these products

on rangeland or on lands in other dryland crops

or under irrigation, and subsequently developing

the products, should be examined. Guayule and jojoba, which already are cultivated in certain areas

of the United States, will be important models for

arid/semiarid land plant development.

Developing cultivation techniques for arid and

semiarid land plants and fulfilling labor requirements need attention. Certainly there is a great need

for a dryland crop to replace irrigated agriculture

in Oklahoma, Nebraska, and western Kansas. However, such crops will be adopted only when markets

for them are established. Crops requiring a high

level of processing, such as milkweed, will be less

readily accepted than crops requiring minimum

processing.

Milkweed development is such that large-scale

production probably is needed to make it economically viable. Large amounts of milkweed are necessary to produce relatively small amounts of the

more valuable products. The ability of a small, locally based industry to establish a milkweed stand and

develop the variety of markets necessary to make

milkweed financially viable is questionable. Scaling-up milkweed processing to make it commercially viable perhaps is the greatest constraint. Private

enterprise may not be willing to take the risk, and

capital available for small-scale venture activities,

even in local communities, is scarce. Processing

must be developed at the same time as milkweed

is being produced. Timing the different aspects of

production is crucial.

The toxicity of milkweed is a problem because

the plants must be processed before use and the

chance of spoilage during storage is increased.

Milkweed’s profitability and, thus, competitiveness

with dryland wheat depends on inositol and pectin, two products that are difficult to extract and

purify. Since these are high cost/low demand products, a balance must be found between the amount

of milkweed needed to make the processing plant

economically viable and the amount needed to supply, yet not flood, the inositol and pectin markets.

Introducing milkweed as a monoculture would

tend to favor vertically integrated companies, large

scale farmers, and rental land tenure arrangements.

More information is needed on the use of milkweed

as a livestock feed and its degree of competitiveness

with feed corn, silage, and grain sorghum. Vertical

integration from cultivation of milkweed to processing would be necessary and farmers have to

have an assured market for milkweed.

A large amount of investment, probably from the

public sector, will be necessary before milkweed

can become a viable choice for U.S. farmers. The

high degree of processing probably will preclude

its use as a crop in Third World countries. Milkweed must be examined in comparison with alternative crops, particularly those crops requiring less

processing, before large public investments are

made. Unless simple machinery, fewer products,

and a tight link between cultivation and processing can be developed simultaneously, it is doubtful that U.S. farmers will benefit from cultivating

milkweed.

Strategic and Essential Industrial

Materials From Plants-

-Is and Uncertainties

by Howard Tankersley and Richard Wheaton

This paper raises important issues about the public sector’s interaction with farmers producing raw

materials and processors processing the materials

for national and international markets. Domestic

production of strategic materials, which are unavailable or in short supply, would be advantageous

to the United States. Because no domestic industry

to process these products exists, government support will be crucial. The U.S. Defense Department

contract which has supported development of guayule as an alternative to natural rubber is an important example of government support for new

crops.

For U.S. industry to be supplied with sufficient

quantities of these-materials, ‘farmers must be assured of a regular market for their products. Bankers and other lenders must be willing to give longterm credit to farmers investing in new crops that

take a long time to establish. Government must

work closely with local bankers to guarantee such

long-term credit arrangements. Farmers may be
Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals . 239

motivated to change to strategic crops, particularly grain farmers in dryland areas of the United

States, but current lending procedures and debts

of the U.S. farm population suggest that without

credit advantages such crop shifts are unlikely to

take place.

The paper points to the necessity of subsidizing

industries to develop these substitutes. However,

subsidies for farmers, particularly as credit and applied research, will also be important, The high cost

of price supports for the major commodities in the

United States suggests the need to move quickly to

subsidize alternative crops that ultimately may not

need so large government inputs in the future.

Because nonexistent crops have no political power, there is little pressure for government involvement in them. Whereas the consumer would be the

ultimate beneficiary of many of these alternative

crops, consumers are not well organized pressure

groups. It will be important to enlist the assistance

of already organized groups whose welfare will be

affected to gain political support for these projects.

Commodity programs are the outcome of efforts

by farmers and their organizations such as the

Farm Bureau, Farmers Union, and the National

Farmers’ Organization. These organizations must

be included in the early stage of crop substitution

planning to assure that farmers’ interests are protected, It might be useful to work with commodity

groups, particularly those representing commodities grown in areas where new crops might be

developed.

It would be interesting to look at the tax writeoffs

available for planting jojoba to see their scope and

to whom they apply. Generally the farm family does

not profit from farming tax writeoffs and ultimately these kinds of tax subsidies encourage more absentee ownership.

It is important that U.S. foreign policy and U.S.

domestic agricultural policy be consistent. Although farmers and USDA are moderately powerful in determining domestic policy, the State

Department seems to be able to override their decisions when foreign policy concerns arise.

It takes a long time to develop a new crop, Farmers are disadvantaged because they absorb production risks and often are not paid for the year’s production until the end of the growing cycle. Because

new crops will take several years to become established, alternative sources of incomes for farmers

during this initial period must be sought. Research

on alternative crops should include work on intercropping or other mechanisms that can provide a

regular income while the crops are being established,

The labor demands for crops such as guayule

have not been discussed or evaluated in the Tankersley and Wheaton paper. It is important to see

if the introduction of these alternative crops would

create a new class of seasonal farm laborers or result in the creation of a smaller, year-round labor

force. Alternative crops could help revitalize rural

communities, particularly if the processing could

be done locally. Will guayule rubber be processed

in existing plants? Will intermediate processing

take place near the point of production?

To assess alternative crops further, it is important to analyze the vested interests of each crop and

its byproducts. For example, the importers of newsprint and paper, which kenaf would displace, may

try to influence legislation. The kenaf experiment

deserves close attention.

Commerically oriented research clearly is necessary and cooperative efforts between USDA, land

grant university scientists, private development

firms, and private industrial producers should be

considered. Government support of research in all

these sectors probably will be required. A dynamic

capitalist system requires that the government can

assume the risks of production in order to establish

a profitable industry. Profit is correctly seen as

belonging in the private sector, risk as belonging

in the public sector.

It is vital that researchers work not only with

farmers but with the end product producers to assure that breeding and selection meet the needs of

production. This will help to provide a ready market for what farmers grow. A screening and breeding program for alternative crops would be very

beneficial and could help strengthen ties between

farm organizations and potential growers and industrial users. Clearly a coordinated government

effort in appropriate agencies is needed for supporting R&D that may ultimately make these products

commercially viable.

Historically, producing material has been less of

a problem than processing the material. Industry

seems more rigid than farmers in shifting products

and techniques. Industry also seems less willing to

take risks than farmers, who are accustomed to

risks.

The shift in developing countries away from nonfood export crops might increase the availability of

prime land for food production. These countries

suffer from enormous balance of payment problems. A shift back to food, particularly if it could

be coupled with the use of locally available

pesticides and fertilizers in a mixed cropping

system, might reduce dependence on foreign food

imports, increase the foreign exchange balance,
240 ● P/ants: The Potentials for Extract/rig Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

and increase the economic and political stability of

many of these countries. However, it is important

to realize that the international grain trade and the

multinational corporations controlling it benefit

greatly from this food dependence and from surplus grainstocks in the United States. In the grain

trade, as much profit is made from shipping as from

the sale of the actual products, and a great price

fluctuation caused by a world market instead of a

local market increases profits. The grain trade may

be a potential opponent of shifting to multiple crops

and increasing self-sufficiency, both in the United

States and Third World countries.

A shift to food production in Third World countries often benefits small farmers, and might result

ultimately in income redistribution both in rural

and urban areas. Such a shift would decrease government’s desires to subsidize cheap food because

soft credit on food imports would no longer provide an artificial underwriting of food costs. That

might lead to increased food costs in Third World

countries, but those costs might be offset by increased food production and increased income,

particularly to rural areas.

Prototype processing plant development should

be undertaken as part of substitute crop development. However, such plants should be encouraged

as joint government/private sector ventures, rather

than simply government prototype plants. The investment of private industry will help increase their

commitment to using the plants.

The variety of mechanisms available to the government to discourage imports and subsidize shifts

in production needs to be fully examined. The wide

variety of tax incentives and disincentives should

be looked at before direct tariff protection or import negation is undertaken.

An arid plants experiment station might be called

for to develop these products more fully. This experiment station should be staffed with more than

agronomists and plant breeders and include people who might apply these products to industrial

and nonindustrial uses based in the same area,

Private firms might be encouraged to rotate personnel to these experiment stations/pilot plant areas

in order to be fully involved in the development

process.

The USDA Economic Botany

Laborator y's Data Base on

Minor Economic Plant Species

by James Duke

The data set of the USDA Economic Botany Laboratory could be valuable for any kind of experiment station breeding, selection or processing program. The case for a wide ranging, well documented data base is made strongly in this paper,

and the amount of Federal dollars spent to support

the program properly would be justified by the

large savings made through information provided

by the data base.

The funding for such a data system is important.

This system should be on-line and linked to experiment stations throughout the United States. Further, informational linkages should be obtained

with CGIAR (Consultative Group on International

Agricultural Research) to avoid duplication of basic

research and encourage greater use of existing information. A comprehensive, up-to-date, and flexible data base such as the one represented here is

essential for organizing and making the vast

amount of existing data available to users. One of

the problems of the system is that it is little known.

Knowledge, use, and support of this system must

be expanded.

The potential value of data on ecological amplitudes of pests and diseases is very important for

breeding programs. That file could save scientists

thousands of hours of work. Millions of dollars for

farmers and consumers could be saved if such data

were put to use.

Information Gathering and Data

Bases That Are Pertinent to the

Development of Plantby Norman Farnsworth and William Loub

While Dr. Duke’s paper deals with a wide variety of characteristics, Dr. Farnsworth’s paper focused on drugs. The same arguments on cost effectiveness of data bases apply to Dr. Farnsworth’s
P/ants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals . 241

paper as apply to Dr. Duke’s paper. The potential

for avoiding costly mistakes by making both positive and negative research results available are increased by such data bases if they are on-line and

available.

That data base would inform both processors and

consumers, creating demands that farmers could

then fulfill through shifting crop production. One

of the crucial issues here for farmers is the difference between monoculture and mixed farming

systems, The tendency in the United States has

been towards monoculture. While this had certain

elements of management and capital efficiency for

farmers, it also increases farmers’ risks through

dependence on single commodities that tend to be

overproduced in this country and worldwide. One

of the important aspects of alternative crops is not

that there will be a single miracle crop that will save

the family farm, but that increased diversity available to American farmers will decrease the dependence of U.S. consumers on imported goods, particularly chemical products that will result both in

lowered prices and higher quality. This increased

diversity for farmers will in turn help U.S. taxpayers by decreasing the bills currently incurred

for subsidizing the basic few commodities that are

the focus of most U.S. production research.

It is important to remember, however, that those

commodities are the basis of U.S. agriculture as we

know it today. Alternative crops that can either be

alternated or intercropped with our current crops

would be an asset. Industrially, looking at crops that

can interdigitate with or complement these crops

on an industrial basis would also be important. For

example, the kinds of botanical pesticides and products that can be used to coat grain for storage and

reduce grain storage loss as insecticides might be

an important kind of crop to consider in areas of

high grain production and storage.

Whereas the use of plants as chemicals seems to

have a ready market, health needs are less often

translated into products because often the sickest

people, as the hungriest people in society, have less

effective demand. One of the roles of the government sector is to try systematically to meet the

needs of those that are disadvantaged in a variety

of ways. An important example of the positive role

of the state is pointed out by Dr. Farnsworth. Japan

and West Germany are active in the botanical pharmaceutical area. The close link between the public

and the private sector in this is crucial for understanding its success.

One of the other issues that has impact on plant

development is that of patents and right restrictions

affecting ability to make a profit. It is clear that from

farmer to processor to marketer, if a profit cannot

be made at each step, a new crop or a new product

cannot be introduced, whatever its potential largescale societal benefits.

For this project to be successful, a close partnership with industry must occur. Again, government

must act to further that link without creating a monopoly that is disadvantageous to the consumer.

The potential of botanical based medicines seems

very high, It is also diversified. There is no one crop

that will provide all the answers. This fact alone

implies a systematic basic research program that

involves careful screening and careful analysis

prior to the undertaking of any project. The data

bases described by Drs. Duke and Farnsworth seem

basic to this process. Research that is government

supported must be part of building a cumulative,

collective undertaking, even though each discovery

of course is that of individual scientists. Individual

scientists must be assured access to the data bases

so that they can be then implemented in further development. It is crucial that such research be related to potential use and use be related to manufacture and marketing. Government has an important

role in establishing and subsidizing such linkages.

1. Research on alternative uses of plants, if combined with applied research on processing and marketing, could be very beneficial for the North

American farmer and U.S. taxpayer, and, if the

processing were relatively simple, to Third World

farm families as well. Such crops would increase

the diversity and self-sufficiency of farms and nation-states.

2. Research and development will need strong

government involvement, through tax incentives

and direct subsidies. Direct subsidies are especially important if less advantaged farmers and firms

are to become involved in developing these new

crops and products. They should be included not

only to encourage better distribution of the benefits

of the enterprises but because such units are more

likely to make more radical changes because of

their relative precarious situation.

3. Labor requirements and location of processing

plants need to be assessed carefully. Such diversified crops and industrial processes have a great potential for furthering rural development in the

United States and community development in

Third World countries. In both cases, local government must be involved. Federal help in making
242 . Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

these links might be the catalyst needed for such

development to occur.

4. Educational programs to increase awareness

of the potential of new crops should be carried out,

perhaps through government supported seminars

coordinated through the USDA cooperative extension service. Established interest groups need to be

persuaded that new crops or products ultimately

will benefit their constituents. Minority entities,

such as Indian nations, are particularly important

beneficiaries of arid land plant development and

need to be included as participants in the development of an arid land plant program.

5. Research in this area should continue and be

better coordinated. The data systems described

need increased support and to be linked to ongoing scientific activity and industrial R&D efforts.

Personnel and computer funds must be appropriated in this area. The land grant universities and

the USDA should be incorporated early into this

research network. Not only will this improve the

quality of the research but will ensure that an established lobbying group has a stake in the program.

6. Coordination of government agencies—including the Food and Drug Administration, USDA, Department of Defense, Department of State, and

others—is important for the full development of

alternative crops. Liaisons should be formed with

appropriate agencies.
ECONOMIC PERSPECTIVE OF INTRODUCTION OF NEW CROPS

(A Review of the OTA Workshop Papers)

Frederick L. Mann

College of Agriculture, University of Missouri, Columbia

introduction

The commercial development of a new product

from a new crop, a new product from a known

crop, or a substitute for an established product requires that a system involving three major subsystems be established: production, processing/

marketing, and consumption (PMC). Each of these

subsystems has a number of functional components, all of which must be in place and operating

viably for the system to function effectively,

Historically, work on new crops has concentrated

first on production technology, with only a general, and often somewhat vague, vision of the structure and magnitude of demand. Obviously, technological aspects of crop production must be researched, but demand and consequent costs and financial returns are just as critical,

Demand analysis and quantification are difficult

to deal with at early stages of product development

because there is a lack of data. Early critical input

into decisions about making additional R&D or

commercial investments can be provided by information gathered from experiences in other countries, similar existing products, and production

technology research which will begin to generate

some cost component information.

A number of possible economic benefits must accrue at various levels of the PMC system for successful introduction of a new crop/product. Benefits must accrue at the farm level; the marketing/

processing level; and, for the government to cooperate in policy and/or R&D resources, at the national economy level. Some possible benefits at

these different levels are listed in table 1. Whether

a crop becomes profitable or not depends on more

than the quantification of economic payout. Figure

1* shows the components of PMC Systems, demonstrating the wide range of possible economic

variables involved in a PMC System.

In the past when new crops became commercial,

the development of the system relied primarily on

entrepreneurship, risk capital, and time. If one

looks at crops that have been introduced and subsequently commercially developed in the United

States within the last 50 years, one finds that there

were one or a few key individuals or institutions

who were convinced that the crop had a future and

did not give up; for example, it was Mr. A. E. Staley

for soybeans (processing); a couple of seed companies for sunflower; USDA and Texas A&M Sorghum Breeders for grain sorghum; and a few California avocado (hobbyists) growers for avocado.

These are what we might call “commodity champions. ”

If new crop research were to follow a more integrated approach, carrying out economic analysis

simultaneously with technology research and constraint identification and analysis, profitable crops

could be expected to be introduced in less time and

at less cost. Demand and profitability analysis for

the entire system, not just cost of production and

partial product analyses, are needed.

The three following possible types of prefeasibility economic determinations should be made prior

to the prototype stage:

1. In the case of import substitution or an alternative crop for an existing product: Is the price

of the end product increasing at or above the

rate of inflation?

2. Does the product have a high income elasticity of demand—i.e., as consumers’ incomes increase do they allocate increasing proportions

to that product?

3. Is there self-perpetuating demand for a new

type of product—e.g., health foods?

Figure 2, “PMC System Decision Matrix, ” was

developed in the NSF study on “Feasibility of Introducing New Crops” to assist in analyzing the

technical, economic, and institutional (regulatory,

policy, sociological, etc.) constraints on production,

marketing (procurement, processing, distribution),

and consumption of new crop products. The matrix

provides an idea of the components involved in

new crop development, which if analyzed would

provide an indication of economic feasibility of the

crop/product introduction.

The discipline of economics never has enough

data to give unequivocal answers, and economic

data are especially limited in the early stages of new

crop R&D. One effective technique to get the best

possible estimates not only of economic but also

technical and institutional feasibility is a modified

Delphi technique. The technique gathers fact and

opinion from all knowledgeable people about a subject, gives values to the judgments, and eventually

arrives at some consensus on the actual situation

regarding the issue. By using the Delphi technique

to gather information on the various components

shown in figure 2, the stage and potential of a crop’s

commercial development can be identified.

Simulation is one of the more comprehensive eco243
244 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

Table 1 .—Benefits That Have an Impact on Economic Feasibility of New Crop Introduction

A. Farm Producer Benefits

1.

2.

3.

4.

5.

6.

7.

8 .

Risk reductio n

Stress toleranc e

Value per acre intensificatio n

Use of marginal land consistent with environmental limitation s

Market diversificatio n

Improved use of family labo r

Improved use of permanent hired labo r

Lower capital inpu t

B. Marketing and Processing Benefits

1. High market demand potentia l

2 . Existing installed processing capacit y

3 . Low processing system cost

4 . Consistent deman d

5 . Product source diversificatio n

6 . Supply security enhancemen t

C. National Economy Benefits

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Import substitutio n

Export market (foreign exchange earnings)

Productive use of otherwise marginal resource s

Adaptable to natural resource conservation practice s

Relatively low energy requirement for production and processin g

Market diversificatio n

High potential impact magnitud e

Impact in areas with limited alternative s

Strategic or essential supply security (risk reduction )

Employment generatio n
Economic Perspective of Introduction of New Crops • 245

Figure 1 .—General PMC Systema

Institutional, Economic, Political, and Social Environment

Taxes, Policies, Legal Requirements, etc.

OUTPUTS

Markets

for

Inputs

Employment.

Returns

on

Investments

Tax

Revenues

Competition

Wastes

Heat

etc.

etc .

MARKETING

Procurement

Elevator Operate

Buyer, Trader,

etc .

Raw

Material

Refined

Products

Processing

Packer ,

Processor ,

etc .

Distribution

Wholesaler ,

Retailer ,

etc .

Consumer Products

CONSUMPTION

I

1

1

INPUTS

Land

Water

Struc -

tures

Equipment

Mater -

ial s

Energy

Trans -

port

Tech -

nology

Labor

Manage,

ment

Financing

Informat ion

etc.

“Demand’* or flow of market signals

.

“Supply“ or product flow

a

From NSF study
246 ● Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

\

Figure 2.—The PMC System Decision Matrixa

P 1

P 2

P 3

P 4

P 5

P 6

P 7

P 8

P 9

P10

P ll

P12

P13

P14

Pl5

P16

Land & water resources I, Production financing I

Pest contro l

Seed availability

Fertilizer needs

Input procurement

Farmerst risk ta.k’ng

Fa= machine- needs

Farm energy r~quirements

,

I

Input information

Go; ft services & regulation I

Ag research programs

Ag information programs

Crop organizations

Famn labor need s

Market info for farmers

Mal Procurement resources

Ma2 Dependable supply I

Ma3 Procurement financing.

Mad Gov’t semice & regulation [

Ma5 Market intelligenc~ I

Ma6 Transport & storage

-

Mbl Processing resources I I

Mb2 Processin~ equipment

I I

I

Mb3 Commodity institutions

Mb4 Processing energy I I Mb5 Processin~ research

Mb6 Processin~ info programs I I

Mb7 Processing by-products

Mb8 Managerial ability 1

I i I I

McI Distribution resource s I I I I

14c3

Mc2 Distribution financing

%oduc.marketinfo ~I

Mc4 Product transportation I I I

Mc5 Market R &— D ‘ r Mc6 Gov ? t services & re~ulation I I I 1 1 , I

C 1 Market penetration I

C 2 Market size I ,

C 3 Consumer awareness 1

C 4 Product versatility

aFrom NSF study.
Economic Perspective of Introduction of New Crops ● 247

. — .

nomic analysis methodologies for determining

feasibility of marketing/consumption components;

farm budget analysis can be used effectively at the

farm level to determine production feasibility.

Finally, to make effective use of the results of

analyses and knowledge base for a particular crop,

a formalized strategy for moving into the commercial production stage can be formulated using a

technique called critical path programing. An example for kenaf from the NSF study is shown in

figure 3.

Some additional observations on economic issues

or constraints to new crop introduction are:

1. Lead time and development investments often

are long and heavy, and risks are high because

of the highly sophisticated nature of much new

product development in the chemical, medical,

pharmaceutical, and refined proteins areas. A

concerted effort is needed to develop an effective partnership between government and the

private sector to share in both the risks and the

benefits.

2. The degree to which a new crop’s development

system is vertically integrated affects how well

synchronized the establishment of the required

subsystem components will be,

3. Many of the products that have been discussed

at the workshop are subject to the “lumpy investment” syndrome in which large investments are needed to incorporate changes in

production. These crops require much greater

knowledge of the economic risks than crops for

which investment increments follow a fairly

smooth curve.

4. Interest groups and government should join

together to form a “New Crops Council.”

5. Existing food crops in developing countries are

usually produced at no more than 30 to 40 percent of the potential of the land base. Food

needs are more likely to be met by improving

the ability to grow known crops than by introducing new crops,

6. Products derived from wild stands give commercial value to plants that previously had only

local or no value. As demand increases, the

cost of the raw product will increase. Once the

demand for a product with a limited market

and high price is satisfied, the product has near

zero value. Production and demand can easily fall out of phase,

Following are the author’s comments from an economics perspective on each of the papers presented

at the workshop.

An Alternate Use for Tobacco

Agriculture: Proteins for Food

Plus a Safer Smoking Material

by Samuel Wildman

As in the case of many new crop development

efforts, this presentation is long on technical process and short on economic feasibility. The shortage

of protein in a global sense has to be considered

in economic terms if it is to be solved. Demand

varies according to the type of protein and whether

it is for specialized use, animal use, or general

human consumption. With specialized uses and animal use, the product must be able to compete with

alternative products in price, availability, and ease

of use, With human consumption, it also must compete with other products on the basis of consumer

taste preference.

According to Wildman’s paper, tobacco protein

extracts have two major specialized uses: for specialized diet requirements and as a protein fortifier

in the packaged foods industry. Although no information on market size is given, the demand for tobacco protein in specialized diets probably is quite

limited. Processing requirements raise serious

questions about the economic viability of protein

extraction solely for this specialized product. Thus,

economic feasibility probably depends on whether

the other subproducts can compete in other protein markets.

Protein fortification in the general package foods

industry is highly dependent upon final consumer

demand. How much more will consumers pay for

a protein fortified packaged food? Available evidence suggests that they will pay only marginally

more because consumers of packaged foods generally have the purchasing power to get adequate

protein from preferred sources, particularly meat.

Thus, for this market, price becomes a prime element of economic feasibility. The paper does not

provide adequate price information to evaluate the

protein’s competitiveness in this market, although

the information provided suggests that its economic

viability is somewhat doubtful, More economic information is needed before the technology’s viability can be assessed.

Since the pricing of green sludge and green residue in the animal protein market depends largely

on the price structure of the higher value products

and the magnitude of the market, their competitive

position is speculative. (The green residue would

be used mainly for deproteinized cigarette tobac-
248 . Plants: The Potent/a/s for Extracting Protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

A . i

.

.

+
Economic Perspective of Introduction of New Crops ● 249

co, so one would assume it would be used as animal

feed only when there is surplus.) If only limited

amounts of these animal feed byproducts are available, compared with the massive market volume for

their established competitors, it is unlikely that the

feed industry would be willing to go to the trouble

and expense of using minor and/or intermittent

amounts of these new products.

In addition to the fortification of packaged foods,

the other possible market for human consumption

is as a protein supplement for populations that do

not have the purchasing power to obtain adequate

protein from preferred sources. This probably

would have to be part of government programs. The

history of attempts to market a protein additive for

home prepared foods such as soups and stews as

a means of increasing proteins in poor peoples’

diets is abysmal.

Poor people on their own often will not buy protein supplements to add to their food, partly

because being poor often is coincident with a low

level of knowledge and commitment to nutritional

needs. Even premixing protein in products bought

by poor people has not had significant results.

Witness attempts at lysine fortification of rice in

Latin America, where housewives often pick out

and throw away the slightly off-color lysine rice

grain. Attempts in Latin America to encourage low

income families to use the protein supplement

INCAPARINA so far have been largely unsuccessful. Raising incomes may well be a more viable

means of achieving nutritional goals.

In many developing countries, poor people suffer from calorie as well as protein shortages; often

the small amount of protein consumed is converted

to energy. The first nutritional requirement is to

raise energy intake levels; otherwise much of the

benefit of increasing protein intake is lost.

The following economic questions need to be answered:

1. In the United States, it is questionable whether

the use of tobacco plants-for protein extracts

2.

3.

will have significant impact on the net income

per acre or the expansion of farmers’ acreage

in tobacco because after the protein has been

extracted, tobacco processors would use the

residual fibers to fulfill the demand for cigarette production.

Investment in commercial processing for tobacco protein is a “lumpy investment. ” In order to accept the risk of investing in an expensive process change, good knowledge about the

economics of the enterprise must be available.

The paper presents no economic information

about competitiveness of tobacco compared

with alternative feedstocks, except to suggest

that total biomass per hectare is high compared

with many alternative crops. That is not sufficient information to determine tobacco’s competitiveness.

A commercial operation may be economically

feasible, but the paper has not shown this, even at

a prefeasibility level. A serious analysis of the entire PMC system for this crop/product is urgently

needed before additional resources are invested in

its development.

Loaf Protein Extraction

From Tropical Plants

by Lehel Telek

Many of the same economic questions arise with

this paper as with Wildman’s. This paper also deals

almost exclusively with technology and very little

with demand, market, costs, and returns, a major

weakness in most publicly and some privately

funded new crop/product research. Original project design should include resources to do initial and

subsequent periodic assessments of economic and

institutional factors determining the feasibility of

the entire PMC system upon which successful commercial development of the new crop/product depends. The additional cost for such economic/institutional analyses would be marginal, and the savings could be enormous.

Although this paper primarily addresses the animal protein market, human consumption also is

contemplated. The comments made on Wildman’s

paper relating to human consumption are relevant

to this paper as well. The LPE process explained

in this paper appears to be much more feasible for

animal protein production than the extraction process for tobacco. Because the protein extract from

the LPE process would be used mainly as animal

feed, it probably would be more competitive with

alternative sources than with tobacco extracts.

Major weaknesses in the overall concept of processed leaf protein for animals in tropical areas need

to be taken into account. There are a number of

tropical crops that already are well-established and

can be consumed directly by animals, even nonruminants. Although direct consumption may not

permit the fine tuning of protein balance needed

for optimum feed conversion ratios, this may not

be so important in tropical areas as in the U.S.

where conversion ratios are critical to profitability. In developing countries where opportunity cost

of labor is low and conversion efficiency may be

less critical, considerable improvement can be
250 ● Plants: The Potentials for Extracting protein, Medicines, and Other Useful Chemicals—Workshop Proceedings

made in animal productivity through direct consumption of many existing, well-established crops.

Marginal improvement in productivity of these

crops and in their use in animal feeding could be

achieved without introducing a processing technique requiring what would bean enormous capital

investment in a developing country, as well as specialized knowledge. It seems unlikely that many developing countries will have either the institutional

capacity or the economic capacity for large scale

processed protein production and use for many

years. These countries might be better advised to

put scarce resources into improving animal feeding

systems based on existing local products for direct

consumption before new systems are introduced.

Again, having said this, there probably are areas

of the tropical world that are ready for processed

leaf protein. Puerto Rico may be one. Nevertheless,

there is insufficient information to determine the

economic feasibility of the system at present.

The Role of the AIkaloid s

of Catharanthus Roseus . . . .

by Gordon Svoboda

Obviously, marketing alkaloids from the Madagascar periwinkle has been successful. If the divergence between general belief and actual fact about

profitability of this cancer drug is as great as

Svoboda suggests, some mechanism to counteract

misinformation is needed to make venture capital

aware of the profit potential of drugs from plants.

Some economic factors incident to this new crop/

product area are:

1.

2.

The research process to arrive at the point

reached for the Madagascar periwinkle is long

and high risk. A partnership between government and private industry, where risks of

“blind alleys” are shared, could stimulate more

activity in the development of pharmaceuticals

from plants.

Some public/private industrywide mechanism

should exist for allocating resources to screening potentially valuable plants, including a

standardized system for reviewing crops that

merit further research. Resources for research

are allocated in a somewhat random and discontinuous way at present.

3. Government regulation of the drug industry,

while admittedly in the public interest, has

raised the cost of product development and

testing until the economic feasibility for many

product markets is questionable. Economic efficiencies in the system can be achieved by

streamlining compliance with and application

of Government regulations, greater use of public resources for product R&D, and earlier attention to economic issues by the product developer.

Chemicals From Arid/Semiarid

Land Plants: Whole Plant Use

Of Milkweeds

by Robert Adam s

This paper generally is responsive to the need for

applying economic criteria to determine feasibility of new crop introduction. It points out the relative economic advantages of crops with the potential to produce several byproducts of economic value. It also highlights the advantages of looking at

crops that do not compete in the same marketplace

with domestic crops; some milkweed byproducts

compete only with imported products. The paper

also attempts to determine comparative advantage

of milkweed production in semiarid areas now producing grain sorghum and wheat.

Because there is a lack of knowledge about processing costs for many of the extracts, their farm gate

value is speculative and their economic feasibility

cannot be predicted yet with any certainty. Nevertheless, the author is to be commended for making

this early effort at determining economic feasibility at the production subsector level of the PMC system. Similar efforts, perhaps using the Delphi technique, need to be made for the marketing and consumption subsectors. Efforts at economic data improvement are imperative.

Insecticides, Insect Repellants,

and Attractants From Arid/Semiarid

Land Plaints

by Martin Jacobso n

The paper provides intriguing information about

seven crops that produce extracts with insecticidal

properties. No economic information is provided

for any except some yield and price information

on neem tree products (oil and cake) in India. Apparently the author recognizes that unless some of

the more valuable neem extracts can be efficiently

produced and marketed, it is not an attractive income crop for a farmer who probably would earn

very little from the harvested seed per tree per year.

Economic screening of the plants described is a

necessary next step in determining which of them
Economic Perspective of Introduction of New Crops ● 251

have economic potential. Applying the PMC systems analysis and using the Delphi technique to improve reliability of the data base could be quite helpful in making these economic choices.

Molluscicidal and Other Economic

PotentiaIs of Ended

by Aklilu Lemma

The information provided in this paper reflects

the usual bias in new crops research; it emphasizes

technological aspects although it recognizes the

need for economic analysis.

This paper appropriately points out the potential

for developing countries of foreign exchange savings (import substitution) by using domestically

produced ended instead of importing chemical

molluscicides to control schistosomiasis. Unfortunately, the paper does not provide cost and comparative price data to permit any but the most generalized assessment of economic potential.

A sufficient data base for Ended to permit a reasonably reliable PMC System analysis probably exists, Until a detailed analysis is done, the economic

potential of Ended for the multiple uses proposed

will remain largely speculative.

Marine Plants: A Unique

and Unexplored Resource

by William Fenical

This paper summarizes some important commercial uses of marine algae for food or food supplements, fertilizer, pharmaceuticals, and in biomedical research. The paper also points out the vast untapped potential of marine plants as sources of biomass, pharmaceuticals, agricultural chemicals,

food and food products, and industrial chemical

feedstocks. Economic obstacles alluded to include

high basic research costs of screening, bioassay,

isolation, synthesis, etc.

Implications are that costs and risks of not being

able to isolate commercially exploitable products

are so great that only with appropriate joint public/private efforts can the potential in pharmaceutical use of marine plants be achieved. For new

pharmaceutical uses, present slow progress likely

will continue unless the United States makes a

public policy decision to increase investments in

this type of research.

Strategic and Essential Industrial

Materials From Plants-Thesis

and Uncertainties

by Howard C. TankersIey

and 8. Richard Wheaton

This paper presents important preliminary strategic and economic criteria for pursuing national

production potential for reducing dependence on

foreign imports of a wide array of strategic and

essential industrial materials.

In economic terms, the private sector has been

unwilling to act on its own initiative, perhaps

because it perceives the costs and risks of converting to national production as higher than continuing to import the products. Recent rapid increases

in petroleum prices may have altered that outlook

for the private sector, but public policy involvement

probably is necessary to bring about a significant

change of attitude of the private sector. Public

policy decisions must relate to underwriting a part

of R&D costs and assuring priority of U.S. produced

products in the U.S. marketplace. It also may require some innovative arrangements between Government and the private sector concerning initial

investments in industrial plant and equipment.

Government policy actions for these strategic and

essential products clearly are key factors in determining economic feasibility.

Information Gathering and Data

Bases That Are Pertinent to the

Development of PIant-Derived

Drugs

by Norman Farnsworth

and William Loub;

and

The USDA Economic Botany

Laboratory's Data Base on Mimer

Economic Plant Species

by James Duke

Both of these data bases are important to furthering production and processing research in the new

crops area. However, neither data base focuses on

economic data.

Since economic data become outdated more rapidly than production, biological, and processing
252 Ž Plants: The Potentials for Extracting Protein, Medicines, and Other Useful Chemicals— Workshop Proceedings

data, it is more difficult to deal with. However, a

central economic data base could be quite helpful

in encouraging both public and private sectors to

invest in further development of promising new

crops and products.

Again, until higher public sector priority is accorded to new crops/products development and reflected through increased R&D funding and appropriate policy actions, it is doubtful that there will

be much change in the area of new crops development.

1.

2.

Conclusions

For a more coordinated and sustained focus on

problems and prospects of new crops/products

development, a representative private/public sector group needs to be established at the national

level. A “New Crops Council” could:

1) be a clearinghouse for information, 2) provide

guidance in establishing priorities, 3) enter into

direct R&D, including initial commercial production, for new crops/products with sufficient technological, institutional, and economic promise,

and 4) review areas of public policy that inhibit

dynamic private involvement in the R&D process, and provide solutions to these.

The scientific community itself appears to have

some attitudes that tend to dampen private and

public sector enthusiasm for developing natural

products derived from plants. The bias is toward

synthetic organic chemicals and related fields.

This reaches into the upper echelons of public

and private sector management. If the many apparently sound economic, developmental, and

societal arguments for more intense efforts at expanding our useful crops and plants base are valid, a well-coordinated educational process is in

order. The public sector should take the initiative

in such an educational effort.

3. Past and ongoing efforts at new crops development tend to focus on production and technological process factors, with little or no early attention to economic factors. Although there usually is some general economic rationale for looking at new crops and/or products, that rationale

seldom is tested either empirically or with simulated information, A relatively reliable and low

cost method for early analysis of economic potential, and identification of elements requiring

in-depth economic analysis, was developed in the

NSF study referred to earlier. All research projects on new crops should include resources to

carry out a PMC Systems analysis at a very early

stage, with required periodic updating of information and analysis. The Delphi technique can

provide meaningful economic information at a

very early stage in research on new crop production, processing, and use.

U. S . GOVERNMENT PRINTING OFFICE : 1983 0 - 24-503