Impacts of Applied Genetics: Micro-Organisms, Plants, and Animals April 1981 NTIS order #PB81-206609 Library of Congress Catalog Card Number 81-600046 For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402 Foreword This report examines the application of classical and molecular genetic technol- ogies to micro-organisms, plants, and animals. Congressional support for an assess- ment in the field of genetics dates back to 1976 when 30 Representatives requested a study of recombinant DNA technology. Letters of support for this broader study came from the then Senate Committee on Human Resources and the House Committee on Interstate and Foreign Commerce, Subcommittee on Health and the Environment. Current developments are especially rapid in the application of genetic technol- ogies to micro-organisms; these were studied in three industries: pharmaceutical, chemical, and food. Classical genetics continue to play the major role in plant and animal breeding but new genetic techniques are of ever-increasing importance. This report identifies and discusses a number of issues and options for the Con- gress, such as: ● Federal Government support of R&D, ● methods of improving the germplasm of farm animal species, . risks of genetic engineering, patenting living organisms, and ● public involvement in decisionmaking. The Office of Technology Assessment was assisted by an advisory panel of scien- tists, industrialists, labor representatives, and scholars in the fields of law, economics, and those concerned with the relationships between science and society. Others con- tributed in two workshops held during the course of the assessment. The first was to investigate public perception of the issues in genetics; the second examined genetic applications to animals. Sixty reviewers drawn from universities, Government, in- dustry, and the law provided helpful comments on draft reports. The Office expresses sincere appreciation to all those individuals. An abbreviated copy of the summary of this report (ch. 1) is available free of charge from the Office of Technology Assessment, U.S. Congress, Washington, D. C., 20510. In addition, the working papers on the use of genetic technology in human and in veterinary medicine are available as a separate volume from the National Technical Information Service. Director Impacts of Applied Genetics Advisory J. E. Legates, Chairman Dean, School of Agriculture and Life Sciences, North Carolina State University Ronald E. Cape Oliver E. Nelson, Jr. Cetus Corp. Laboratory of Genetics University of Wisconsin Nina V. Fedoroff Department of Embryology Carnegie Institution of Washington David Pimentel Department of Entomology June Goodfield Cornell University The Rockefeller University Harold P. Green Robert Weaver Fried, Frank, Harris, Shriver and Kampelman Department of Agricultural Economics Halsted R. Holman Pennsylvania State University Stanford University Medical School M. Sylvia Krekel James A. Wright Health and Safety Office Pioneer Hi-Bred International Oil, Chemical, and Atomic Workers Plant Breeding Division International Union Elizabeth Kutter Norton D. Zinder The Evergreen State College The Rockefeller University iv Applied Genetics Assessment Staff Joyce C. Lashof, Assistant Director, OTA Health and Life Sciences Division Gretchen Kolsrud, Program Manager Zsolt Harsanyi, Project Director Project Staff Marya Breznay, Administrative Assistant Lawrence Burton, Analyst Susan Clymer, Research Assistant Renee G. Ford, * Technical Editor Michael Gough, Senior Analyst Robert Grossman,* Analyst Richard Hutton, * Editor Geoffrey M. Karny, Legal Analyst Major Contractors Benjamin G. Brackett, University of Pennsylvania The Genex Corp. William P. O’Neill, Poly-Planning Services Plant Resources Institute Anthony J. Sinskey, Massachusetts Institute of Technology Aladar A. Szalay, Boyce-Thompson Institute Virginia Walbot, Washington University OTA Publishing Staff John C. Holmes, publishing Officer John Bergling* Kathie S. Boss Debra M. Datcher Patricia A. Dyson* Mary Harvey * Joe Henson OTA contract personnel. v Contents Page . Glossary . .. .. .viii Acronyms and Abbreviations . xii Chapter l. Summary: Issues and Options . 3 Chapter 2. Introduction . .......00 29 Part I :Biotechnology Chapter 3. Genetic Engineering and the Fermentation Technologies . 49 Chapter 4. The Pharmaceutical Industry. 59 Chapter 5. The Chemical Industry . 85 Chapter 6. The Food Processing Industry. .. ....107 Chapter 7. The Use of Genetically Engineered Micro-Organisms in the Environment. ......117 Part II: Agriculture Chapter 8. The Application of Genetics to Plants . .. ...137 Chapter 9. Advances in Reproductive Biology and Their Effects on Animal Improvement . 167 Part III: Institutions and Society Chapter l0. The Question of Risk. .......199 Chapter ll. Regulation of Genetic Engineering. .. ....211 Chapter 12. Patenting Living Organisms. ..........237 Chapter 13. Genetics and Society . ................257 Appendixes I-A. A Case Study of Acetaminophen Production. ...269 I-B. A Timetable for the Commercial Production of Compounds Using Genetically Engineered Micro-Organisms in Biotechnology . ........275 I-C. Chemical and Biological Processes. ..........292 I-D. The Impact of Genetics on Ethanol-A Case Study . .............293 II-A. A Case Study of Wheat. .. ...304 11-B. Genetics and the Forest Products Industry Case Study . .........307 II-C. Animal Fertilization Technologies. ..........309 III-A. History of the Recombinant DNA Debate . .. ...315 III-B. Constitutional Constraints on Regulation. .. ...320 111-C. Information on International Guidelines for Recombinant DNA. ......322 IV. Planning Workshop Participants, Other Contractors and Contributors, and Acknowledgments. ...329 vii Glossary Aerobic.—Growing only in the presence of oxygen. volve the use of genetically engineered micro- organisms. Anaerobic. —Growing only in the absence of oxygen. Blastocyst.— An early developmental stage of the embryo; the fertilized egg undergoes several cell Alkaloids.—A group of nitrogen-containing organic divisions and forms a hollow ball of cells called substances found in plants; many are pharmaco- the blastocyst. logically active—e.g., nicotine, caffeine, and cocaine. Callus.—The cluster of plant cells that results from tissue culturing a single plant cell. Allele.—Alternate forms of the same gene. For ex- ample, the genes responsible for eye color (blue, Carbohydrates.— The family of organic molecules brown, green, etc.) are alleles. consisting of simple sugars such as glucose and sucrose, and sugar chains (polysaccharides) such Amino acids.—The building blocks of proteins. as starch and cellulose. There are 20 common amino acids; they are’ joined together in a strictly ordered “string” Catalyst.—A substance that enables a chemical which determines the character of each protein. reaction to take place under milder than normal conditions (e.g., lower temperatures). Biological Antibody.—A protein component of the immune catalysts are enzymes; nonbiological catalysts in- system in mammals found in the blood. clude metallic complexes. Cell fusion.—The fusing together of two or more Antigen.—A large molecule, usually a protein or cells to become a single cell. carbohydrate, which when introduced in the body stimulates the production of an antibody Cell lysis.—Disruption of the cell membrane allow- that will react specifically with the antigen. ing the breakdown of the cell and exposure of its contents to the environment. Aromatic chemical.—An organic compound con- taining one or more six-membered rings. Cellulase.—An enzyme that degrades cellulose to glucose. Aromatic polymer.–Large molecules consisting of repeated structural units of aromatic chem- Cellulose.–A polysaccharide composed entirely of icals. several glucose units linked end to end; it consti- tutes the major part of cell walls in plants. Artificial insemination.—The manual placement of sperm into the uterus or oviduct. Chimera.—An individual composed of a mixture of genetically different cells. Bacteriophage (or phage).–A virus that multi- plies in bacteria. Bacteriophage lambda is com- Chloroplast.-The structure in plant cells where monly used as a vector in recombinant DNA ex- photosynthesis occurs. periments. Chromosomes.—The thread-like components of a cell that are composed of DNA and protein. They Bioassay .–Determination of the relative strength contain most of the cell’s DNA. of a substance (such as a drug) by comparing its effect on a test organism with that of a standard Clone.—A group of genetically identical cells or preparation. organisms asexually descended from a common ancestor. All cells in the clone have the same ge- Biomass.—Plant and animal material. netic material and are exact copies of the original. Biome.—A community of living organisms in a ma- Conjugation.—The one-way transfer of DNA be- jor ecological region. tween bacteria in cellular contact. Biosynthesis. —The production of a chemical com- Crossing-over. —A genetic event that can occur pound by a living organism. during celluar replication, which involves the breakage and reunion of DNA molecules. Biotechnology .—The collection of industrial proc- esses that involve the use of biological systems. Cultivar.—An organism developed and persistent For some of these industries, these processes in- under cultivat ion. Cytognetics.-A branch of biology that deals with Gene.–The hereditary unit; a segment of DNA the study of heredity and variation by the meth- coding