The Terminology of Biotechnology: A Multidisciplinary Problem

A brief history of biochemical nomenclature and the development of joint nomenclature efforts of the International Union of Pure and Applied Chemistry (IUPAC) and the International Union of Biochemistry (IUB) are presented. The organizational arrangement of cooperation between the two unions is described. Results of this setup are listed. Special mention is made of the biochemical compendium and the enzyme nomenclature book, and future projects are outlined. Cooperation with other nomenclature bodies that have overlapping interests is cited, such as with the International Union of Nutritional Sciences (IUNS), and with the International Federation of Clinical Chemistry (IFCC).

Unambiguous identification of organisms and molecules is necessary for science. Our Linnaean inheritance of latinized scientific names for biological organisms allows scientists, geographically dispersed and in different disciplines, in full confidence, to discuss the same organism. However in the rapidly evolving biological sciences and applied biotechnologies, a plethora of novel terms are accumulating. While much of this new vocabulary is indispensable in describing specific processes, novel compounds and organisms etc. many of these terms lead to confusion with existing terminology in a variety of fields. Prevailing guidelines on biological nomenclature and terminology prevent much confusion in the disciplines where they exist. And although many ambiguous terms will simply disappear through lack of usage, standardization of nomenclature should be encouraged where feasible.

The scientific literature contains an increasing number of reports of proteins altered in many different ways. It is becoming evident that a nomenclature system needs to be implemented to bring some order to this research area. Comments and suggestions relating to what such a system should include, focusing on specific recommendations in certain areas, are presented in this report.

Currently there are over 120,000 protein sequences and over 35,000 nucleic acid sequences in the Chemical Abstracts Service (CAS) machine and manual files. Approximately 20,000 new sequences are reported each year. Both the current number of existing sequences and the rapid increase in the number of new sequences being reported require maintaining and developing a nomenclature system to keep up with advances in the field. Clear, unambiguous and unique names are needed in order to keep track of and to report biopolymer sequence information in abstracts, databases, and in indexes. The CAS naming and representation of amino acids, peptides, and nucleic acids including those with both short and long sequences are presented. Problems encountered with altered sequences of natural products, and those with partial sequences or with undefined or ambiguous groups are discussed.

The term “carbohydrate” was introduced early when gravimetric methods of analysis permitted the assignment of empirical formulas and it became recognized that starch, cane sugar, and the fibrous material of plant cell-walls were all comprised of carbon, hydrogen, and oxygen, with the latter elements being present in the same ratio as in water. The German term “Kohlenhydrate” and the French “hydrates de carbone” originated similarly. The generic suffix “-ose” in conjunction with the French “cellule” (for cell) led to the name “cellulose”, the most abundant natural organic compound; however, the constitution of this compound as an acetal-linked linear biopolymer of a polyhydroxyaldehyde monomer was not recognized until some two centuries after its discovery.

For many years there has been an almost continuous series of standing committees, organized by the International Union of Biochemistry or the International Union of Pure and Applied Chemistry, or both, dealing with nomenclature problems specific to biochemists. The present arrangement, described by Kurt Loening earlier in this symposium, is a Nomenclature Committee of I.U.B., and a Joint IUPAC/IUB Committee on Biochemical Nomenclature; the Committees have overlapping membership and normally meet in combined sessions. For most of the time such committees have existed, and certainly since the late 1950’s when I.U.B. set up the original Enzyme Commission under the Chairmanship of Malcolm Dixon, enzyme nomenclature has occupied more of their time than any other section of biochemical nomenclature. In this paper I hope to show why this is so.

Interferons were discovered in 1957 and subsequently divided into antigenically distinct types: type I, represented by the leukocyte and fibroblast types (generally acid stable), and type II, represented by immune interferon (generally acid labile). With cloning of the interferon genes and formation of an ad hoc interferon nomenclature committee, the names interferon-α, interferon-β, and interferon-γ to refer to the pure species that comprise the predominant class of leukocyte, fibroblast and immune interferons, respectively, were proposed and met with general acceptance among the scientific community. The evolution of the current nomenclature system for interferon proteins, recent studies on interferon-β2, acceptance of the term IL-6, and unresolved nomenclature issues in the interferon field are overviewed here.

Hybridoma technology is a relatively new tool for the development of biochemical reagents having wide applicability in many areas of biology and chemistry. These reagents are termed “immunoreagents” because they are produced by cultured cell lines selected for their ability to secrete immunoreactive substances. The most common of these immunoreagents are monoclonal antibodies (MABs), which exhibit complex reactivity patterns although they are specific to unique epitopes. Epitopes are antigenic determinants of specific structure, i.e., chemically active structural components of proteins and complex carbohydrates which interact with antibodies (immunoglobulins). MABs developed through hybridoma technology are highly specific to individual epitope topologies, but because similar epitopes can be found on diverse proteins and polysaccharides, the MABs may react with dissimilar cell types or biochemical substances, despite their definition as “reagents of defined specificity”.

The recent progress in biotechnology, in particular in techniques to manipulate the genetic molecule DNA, has led to probably the most exciting, and also much debated enterprise in biology: to reveal the sequence of the human genome.

Eicosanoids are oxygenated derivatives of polyunsaturated fatty acids (PUFAs), generally of 20 carbons in chain length and often with important biological activity; the PUFAs themselves can be named according to a shorthand nomenclature describing chain length, degree of unsaturation and position of the double bond nearest the terminal methyl (“omega”) carbon. Arachidonic acid (20:4ω6) is the archetypal precursor for all main classes of the eicosanoids. Prostaglandins (PGs) A-J (ring type) are further classified as to degree of unsaturation in the side chains (eg PGE₁ has one such double bond) and also according to stereochemistry; thromboxanes (A or B, according to ring type) have similar nomenclature.

Leukotrienes (LTs) have a characteristic conjugated triene system and are almost always formed via 5-lipoxygenation. LTA compounds are 5(6) epoxides and LTB compounds are characteristic dihydroxy compounds. LTs C-D are peptidolipids each with a specific amino acid characteristically attached via sulfur to carbon 6 of the fatty acid moiety. Lipoxins (LXs) are characteristic trihydroxy compounds derived by 15-lipoxygenation via an epoxy-15-hydroxy intermediate. LXAs have a 5,6-dihydroxy region and LXBs have a 14,15-dihydroxy region. Both LTs and LXs are (like PGs and TXs) subclassified according to degree of side chain unsaturation. Nomeclature of other oxygenated PUFA metabolites (HEThs etc) is logically adapted from previous usage. Nomenclature of PG-like (prostanoid) receptors are classified into EP, FP, DP and TP types whose characteristic natural agonists are (respectively) E-type PGs, F-type PGs, D-type PGs and thromboxane A₂ but are better defined by response to more specific synthetic prostanoids and newly developed specific antagonists. It is now recognized that the EP receptor may be subclassifled into EP₁, EP₂, and EP₃ receptors. Recently, subclassification of peptidoleukotriene receptors has been proposed (PLT₁, PLT_2a, PLT_2b, PLT_2c and PLT_2d) and for LTB receptors (LTB_41a and LTB_41b. Proposals for more accurate nomenclature for enzymes that form anl metabolize eicosanoids are discussed.

The United States Adopted Names (USAN) Council is the United States committee responsible for negotiating nonproprietary names for the pharmaceutic industry. It is a nongovernmental organization sponsored by the American Medical Association, the United States Pharmacopeial Convention, and the American Pharmaceutical Association. Nonproprietary names serve a useful function that cannot be supplanted by the chemical name or trademark. The goal of the Council is to produce simple, short, unique, and useful names that can be used without restriction in the public domain. The Council also has close liaison with the International Nonproprietary Names (INN) Committee of the World Health Organization and works to establish Council-generated names as international names.

Some aspects regarding Japanese Accepted Names (JAN) for biotechnologically-derived pharmaceutical substances are described from the point of view of a regulatory scientist who is engaged in the quality control of these types of drugs, as well as from the viewpoint of a biochemist.

The immune system is composed of a large variety of cells and molecules which are characterized by their diverse biologic functions. In order to describe their generation and the dynamic interactions, meaningful and coherent terminology is absolutely necessary. However, the situation is yet unsatisfactory because of the reasons we describe here. The mother society of immunological organizations, the International Union of Immunological Societies (IUIS), has started a nomenclature committee in 1973, and has organized a series of committee meetings where a standard procedure for immunological terminology has been proposed. The procedure consists of 5 steps: 1) Establishment of a specific committee (working group), 2) development of an initial draft, 3) review by parental WHO-IUIS nomenclature committee, 4) submission of the document to the WHO Bulletin, 5) submission to other journals using the reference from the WHO Bulletin. Several activities are currently on-going (1). However, the problems have become more complicated than the time of above proposal as we describe here, which do not allow the simple application of the above procedure. We shall discuss in this communication how the nomenclature problems have arisen in immunology, and what efforts are being made to solve them. The problems in immunological terminology are probably typical ones which are shared by other disciplines of molecular and cellular biology. Three important areas were chosen to present current movements to establish unified nomenclature in immunology. They are 1) HLA (human histocompatibility antigens) by the International Histocompatibility Workshop and Conference, 2) CD (leukocyte differentiation markers) by the International Workshop and Conference on Human Leukocyte Differentiation Antigens, and 3) IL (interleukins-lymphokines) by the International Lymphokine Workshop and IUIS nomenclature subcommittee.

Historically, biologists have established formal rules for the naming of organisms. The drive to standardize the naming conventions in biology, including microbiology, began long before the advent of computers and the attendant construction of databases. The wish to classify gave the impetus to the creation of procedures and standards for publishing and legitimizing the names of taxa.

Terminological activities in agriculture are active in Japan. Each scientific society has authorized terminology pertinent to the science, taking the style of Japanese -English and English-Japanese dictionary. Pesticide Science Society of Japan also edited such a dictionary. Pesticides, implying ” kill” has given a negative emotion to the public, while new pest control chemicals are often not bio-cides but regulating vital life processes and modifying pest behaviors to exert their action. An ACS division has changed its name to ”Agrochemicals” from Pesticide Chemistry. The corresponding Japanese wording “NOYAKU” has already gotten a negative image. The growing number of chemicals which affect uncoventionally to pests and crops requires newer terminology such as bioregulators, bioregulants, pestistatics, behavior modifyer, behavioral chemicals etc. and provides a challenge to translate them into proper Japanese.

The terminology, symbols and units of physical quantities constitute a major part of “the grammar of science and technology”, by which one can acquire, record, transmit, and digest useful scientific information [1]. Since biotechnology is one of the truly interdisciplinary and international fields of research, it is essential to establish “a standard language of communication” for description of information that can be handled easily and understood correctly by anybody, anywhere, and at any time. Thus proper use of units and symbols of physical quantities is just as important as that of chemical and biological nomenclature.

The present state of evolution of biotechnology as a multidisciplinary field has revealed concerns for real engineering expertise for implementation of the various relevant biology-based techniques. Technical language difficulties are beginning to become apparent. The need to address them by the collective deliberations of professional organizations traditionally devoted to related but separate disciplines is clear.

Modern technology is changing the world in many ways. An important result is our ability to communicate within seconds from every corner of the earth. Thus, more and more importance is now attached to the exchange of information. This growing need for information demands that the data to be retrieved are systematized in such a way that the required information can be retrieved quickly, easily and relatively cheaply. Many on-line databanks exist which can provide the public with many different types of information. In practice however, the retrieval of information from these systems often meets with considerable problems. The possibilities of modern technology and the exponentional growth of the quantity of available information lead among other things to great difficulties in communication. In order to be able to systematize information to be entered into a database, the vocabulary of the subject fields in question needs to be controlled. In biotechnology there is a great need for institutional development of information resources. What is needed is a vocabulary development effort that keeps up with the developments in biotechnology to create an internationally recognized and consistent vocabulary. Assistance in this matter is given by the principles and methods of terminology and computerized terminography.

Biotechnical information on computers presents special terminology challenges for locating and integrating computer data from diverse sources and levels. Standard nomenclature problems such as synonyms, homographs, and name changes are compounded when they arise on computers for names of databases, entities, and variables, as well as data values from multiple independent sources.

At the same time, computers make possible the development of new tools to meet these challenges. The data thesaurus is one such tool that helps integrate different types of data. It provides a systematic framework within which both people and computer programs can reconcile terminology from diverse, autonomous databases. Data thesauri also can help guide evolution of international standards for nomenclature and classification.

The ENCYCLOPEDIA OF CHEMICAL TECHNOLOGY (ECT), a significant reference work for the chemical industry, serves as an instructional aid for scientists and engineers who are generally not specialists in the particular area where they are seeking information. The ENCYCLOPEDIA provides an introduction of a wide range of topics to a diverse readership. Because ECT is both a teaching tool and regarded as an authoritative source, the vocabulary within it must be standardized. Chemical and biotechnological terminology, nomenclature, symbols, units, etc. must be both consistent and accurate.

Biotechnology is not new to ECT. Coverage began with such entries as ENZYMES AND ENZYMOLOGY and FERMENTATION in the first edition and continues through the newest work, ECT-4, which is in preparation for the 1990’s. Constructing ECT-4 means choosing the 1180 article titles, identifying authors, and arranging for peer review, in addition to editing the material and keeping to schedule. This process, together with the requirements for standardizing the scientific vocabulary, will be discussed.

The United States Pharmacopeia (USP) and National Formulary (NF) are the official compendia of drug standards in the United States of America. Standards of the USP and NF also are recognized in the laws of numerous other nations.