BIOTECHNOLOGY INDUSTRY   

 

Susan B. Lee, Linda B. Wolfe

 

 

Evolution and Profile

Biotechnology can be defined as the application of biological systems to technical and industrial processes. It encompasses both traditional and genetically engineered organisms. Traditional biotechnology is the result of classic hybridization, mating or crossing of various organisms to create new organisms that have been used for centuries to produce bread, beer, cheese, soya, saki, vitamins, hybrid plants and antibiotics. More recently, various organisms have also been used to treat waste water, human sewage and industrial toxic wastes.

 

Modern biotechnology combines the principles of chemistry and biological sciences (molecular and cellular biology, genetics, immunology) with technological disciplines (engineering, computer science) to produce goods and services and for environmental management. Modern biotechnology utilizes restriction enzymes to cut and paste genetic information, DNA, from one organism to another outside living cells. The composite DNA is then reintroduced into host cells to determine whether the desired trait is expressed. The resulting cell is called an engineered clone, a recombinant or a genetically manipulated organism (GMO). The “modern” biotechnology industry was born in 1961-1965 with the breaking of the genetic code and has grown dramatically since the first successful DNA cloning experiments in 1972.

 

Since the early 1970s, scientists have understood that genetic engineering is an extremely powerful and promising technology, but that there are potentially serious risks to consider. As early as on 1974, scientists called for a worldwide moratorium on specific types of experiments in order to assess the risks and to devise appropriate guidelines for avoiding biological and ecological hazards (Committee on Recombinant DNA Molecules, National Research Council, National Academy of Sciences 1974). Some of the concerns expressed involved the potential “escape of vectors which could initiate an irreversible process, with a potential for creating problems many times greater than those arising from the multitude of genetic recombinations that occur spontaneously in nature”. There were concerns that “microorganisms with transplanted genes could prove hazardous to man or other forms of life. Harm could result if the altered host cell has a competitive advantage that would foster its survival in some niche within the ecosystem” (NIH 1976). It was also well understood that laboratory workers would be the “canaries in the coal mine” and some attempt should be made to protect the workers as well as the environment from the unknown and potentially serious hazards.

 

An international conference in Asilomar, California, was held in February 1975. Its report contained the first consensus guidelines based on biologic and physical containment strategies for controlling potential hazards envisioned from the new technology. Certain experiments were judged to pose such serious potential dangers that the conference recommended against their being conducted at that time (NIH 1976). The following work was originally banned:

 

· work with DNA from pathogenic organisms and oncogenes

· forming recombinants that incorporate toxin genes

· work which might extend the host range of plant pathogens

· introduction of drug resistance genes into organisms not known to acquire them naturally and where treatment would be compromised

· deliberate release into the environment (Freifelder 1978).

 

In the United States the first National Institutes of Health Guidelines (NIHG) were published in 1976, replacing the Asilomar guidelines. These NIHG allowed research to proceed by rating experiments by hazard classes based on the risks associated with host cell, vector systems which transport genes into the cells and gene inserts, thereby allowing or restricting the conduct of the experiments based on risk assessment. The basic premise of the NIHG-to provide for worker protection, and by extension, community safety-remains in place today (NIH 1996). The NIHG are updated regularly and they have evolved to be a widely accepted standard of practice for biotechnology in the US. Compliance is required from institutions receiving federal funding, as well as by many local city or town ordinances. The NIHG provides one basis for regulations in other countries around the world, including Switzerland (SCBS 1995) and Japan (National Institute of Health 1996).

 

Since 1976, the NIHG have been expanded to incorporate containment and approval considerations for new technologies including large scale production facilities and plant, animal and human somatic gene therapy proposals. Some of the originally banned experiments are now allowed with specific approval from NIH or with specific containment practices.

 

In 1986 the US Office of Science and Technology Policy (OSTP) published its Coordinated Framework for Biotechnology Regulation. It addressed the underlying policy question of whether existing regulations were adequate to evaluate products derived from the new technologies and whether the review processes for research were sufficient to protect the public and the environment. The US regulatory and research agencies (Environmental Protection Agency (EPA), Food and Drug Administration (FDA), Occupational Safety and Health Administration (OSHA), NIH, US Department of Agriculture (USDA) and National Science Foundation (NSF)) agreed to regulate products, not processes, and that new, special regulations were not necessary to protect workers, the public or the environment. The policy was established to operate regulatory programmes in an integrated and coordinated fashion, minimizing overlap, and, to the extent possible, responsibility for product approval would lie with one agency. The agencies would coordinate efforts by adopting consistent definitions and by using scientific reviews (risk assessments) of comparable scientific rigor (OSHA 1984; OSTP 1986).

 

The NIHG and Coordinated Framework have provided an appropriate degree of objective scientific discussion and public participation, which has resulted in the growth of US biotechnology into a multibillion dollar industry. Prior to 1970, there were fewer than 100 companies involved in all aspects of modern biotechnology. By 1977, another 125 firms joined the ranks; by 1983 an additional 381 companies brought the level of private capital investment to more than $1 billion. By 1994 the industry had grown to more than 1,230 companies (Massachusetts Biotechnology Council Community Relations Committee 1993), and market capitalization is more than $6 billion.

 

Employment in US biotechnology companies in 1980 was about 700 people; in 1994 roughly 1,300 companies employed more than 100,000 workers (Massachusetts Biotechnology Council Community Relations Committee 1993). In addition, there is an entire support industry which provides supplies (chemicals, media components, cell lines), equipment, instrumentation and services (cell banking, validation, calibration) necessary to ensure the integrity of the research and production.

 

Throughout the world there has been a great level of concern and scepticism about the safety of the science and of its products. The Council of the European Communities (Parliament of the European Communities 1987) developed directives to protect workers from the risks associated with exposure to biologicals (Council of the European Communities 1990a) and to place environmental controls on experimental and commercial activities including deliberate release. “Release” includes marketing products using GMOs (Council of the European Communities 1990b; Van Houten and Flemming 1993). Standards and guidelines pertaining to biotechnology products within international and multilateral organizations such as World Health Organization (WHO), International Standards Organization (ISO), Commission of the European Community, Food and Agriculture Organization (FAO) and Microbial Strains Data Network have been developed (OSTP 1986).

 

The modern biotechnology industry can be considered in terms of four major industry sectors, each having laboratory, field and/or clinical research and development (R&D) supporting the actual production of goods and services.

 

· biomedical-pharmaceuticals, biologics and medical device products

· agricultural-foods, transgenic fish and animals, disease resistant and pest resistant plants

· genetically enhanced industrial products such as citric acid, butanol, acetone, ethanol and detergent enzymes (see table 77.11)

· environmental-waste water treatment, decontamination of industrial wastes.

 

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Table 77.11. Microorganisms of industrial importance

 

Name

Host organism

Uses

Acetobacter aceti

Aerobic bacterium

Ferments fruit

Aspirgillus niger

Asexual fungus

Degrades organic matter

Safe use in production of citric acid and enzymes

Aspirgillus oryzae

Asexual fungus

Used in production of miso, soy sauce and sake

Bacillis licheniformis

Bacterium

Industrial chemicals and enzymes

Bacillis subtilis

Bacterium

Chemicals, enzymes, source of single-cell protein for human consumption in Asia

Chinese hampster ovary cells (CHO)*

Mammalian cell culture

Manufacturing of biopharmaceuticals

Clostridium acetobutylicum

Bacterium

Butanol, acetone production

Escherichia coli K-12*

Bacterial strain

Cloning for fermentation, production of pharmaceuticals and biologics

Penicillium roqueforti

Asexual fungus

Blue cheese production

Saccharomyces cerevisiae*

Yeast

Cloning for beer production

Saccharomyces uvarum*

Yeast

Cloning for alcoholic beverages and industrial alcohol production

 

* Important to modern biotechnology.

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Biotechnology Workers

Biotechnology begins in the research laboratory and is a multidisciplinary science. Molecular and cellular biologists, immunologists, geneticists, protein and peptide chemists, biochemists and biochemical engineers are most directly exposed to the real and potential hazards of recombinant DNA (rDNA) technology. Other workers who may be exposed less directly to rDNA biohazards include service and support staff such as ventilation and refrigeration technicians, calibration service providers and housekeeping staff. In a recent survey of health and safety practitioners in the industry, it was found that the directly and indirectly exposed workers comprise about 30 to 40% of the total workforce in typical commercial biotechnology companies (Lee and Ryan 1996). Biotechnology research is not limited to “industry”; it is conducted in the academic, medical and government institutions as well.

 

Biotechnology laboratory workers are exposed to a wide variety of hazardous and toxic chemicals, to recombinant and non-recombinant or “wild type” biological hazards, human bloodborne pathogens and zoonotic illnesses as well as radioactive materials used in labelling experiments. In addition, musculoskeletal disorders and repetitive strain injuries are becoming more widely recognized as potential hazards to research workers due to extensive use of computers and manual micropipettors.

 

Biotechnology manufacturing operators are also exposed to hazardous chemicals, but not the variety one sees in the research setting. Depending on the product and the process, there may be exposure to radionuclides in manufacturing. At even the lowest biohazard level, biotechnology manufacturing processes are closed systems and potential for exposure to the recombinant cultures is low, except in the case of accidents. In biomedical production facilities, application of current good manufacturing practices complements biosafety guidelines to protect workers on the plant floor. The main hazards to manufacturing workers in good large-scale practice (GLSP) operations involving non-hazardous recombinant organisms include traumatic musculoskeletal injuries (e.g., back strains and pain), thermal burns from steam lines and chemical burns from acids and caustics (phosphoric acid, sodium and potassium hydroxide) used in the process.

 

Health care workers including clinical laboratory technicians are exposed to gene therapy vectors, excreta and laboratory specimens during the administration of drugs and care of patients enrolled in these experimental procedures. Housekeepers may also be exposed. Worker and environmental protection are two mandatory experimental points to consider in making application to NIH for human gene therapy experiments (NIH 1996).

 

Agricultural workers may have gross exposure to recombinant products, plants or animals during the application of pesticides, planting, harvesting and processing. Independent of the potential biohazard risk from exposure to genetically altered plants and animals, the traditional physical hazards involving farm equipment and animal husbandry are also present. Engineering controls, PPE, training and medical supervision are used as appropriate to the anticipated risks (Legaspi and Zenz 1994; Pratt and May 1994). PPE including jump suits, respirators, utility gloves, goggles or hoods are important for worker safety during application, growth and harvesting of the genetically modified plants or soil organisms.

 

Processes and Hazards

In the biotechnology process in the biomedical sector cells or organisms, modified in specific ways to yield desired products, are cultivated in monoculture bioreactors. In mammalian cell culture, the protein product is secreted from the cells into the surrounding nutrient medium, and a variety of chemical separation methods (size or affinity chromatography, electrophoresis) may be used to capture and purify the product. Where Escherichia coli host organisms are used in fermentations, the desired product is produced within the cell membrane and the cells must be physically ruptured in order to harvest the product. Endotoxin exposure is a potential hazard of this process. Often antibiotics are added to the production media to enhance production of the desired product or maintain selective pressure on otherwise unstable genetic production elements (plasmids). Allergic sensitivities to these materials are possible. In general, these are aerosol exposure risks.

 

Leaks and releases of aerosols are anticipated and potential exposure is controlled in several ways. Penetrations into the reactor vessels are necessary for providing nutrients and oxygen, for off-gassing carbon dioxide () and for monitoring and controlling the system. Each penetration must be sealed or filtered (0.2 micron) to prevent contamination of the culture. The exhaust gas filtration also protects workers and environment in the work area from aerosols generated during the culture or fermentation. Depending on the biohazard potential of the system, validated biological inactivation of liquid effluents (usually by heat, steam or chemical methods) is standard practice. Other potential hazards in biotech manufacturing are similar to those in other industries: noise, mechanical guarding, steam/heat burns, contact with corrosives and so on.

 

Enzymes and industrial fermentation are covered elsewhere in this Encyclopaedia and involve the processes, hazards and controls that are similar for genetically engineered production systems.

 

Traditional agriculture depends on strain development that utilizes traditional crossing of related plant species. The great advantage of genetically engineering plants is that the time between generations and the number of crosses needed to obtain the desired trait is greatly reduced. Also the currently unpopular reliance on chemical pesticides and fertilizers (which contribute to runoff pollution) is favouring a technology which will potentially make these applications unnecessary.

 

Plant biotechnology involves choosing a genetically pliable and/ or financially significant plant species for modifications. Since plant cells have tough, cellulose cell walls, methods used to transfer DNA into plant cells differ from those used for bacteria and mammalian cell lines in the biomedical sector. There are two primary methods used for introducing foreign engineered DNA into plant cells (Watrud, Metz and Fishoff 1996):

 

· a particle gun shoots DNA into the cell of interest

· a disarmed, nontumorigenic Agrobacterium tumefaciens virus introduces gene cassettes into the cell’s genetic material.

 

Wild-type Agrobacterium tumefaciens is a natural plant pathogen which causes crown gall tumours in injured plants. These disarmed, engineered vector strains do not cause plant tumour formation.

 

After transformation by either method, plant cells are diluted, plated and grown on selective tissue culture media for a relatively long (compared to bacterial growth rates) period in plant growth chambers or incubators. Plants regenerated from the treated tissue are transplanted to soil in enclosed growth chambers for further growth. After reaching the appropriate age they are examined for expression of the desired traits and then grown in greenhouses. Several generations of greenhouse experiments are needed to evaluate the genetic stability of the trait of interest and to generate needed seed stock for further study. Environmental impact data is also gathered during this phase of the work and submitted with proposals to regulatory agencies for open field trial release approval.

 

Controls: The United States Example

The NIHG (NIH 1996) describe a systematic approach to preventing both worker exposure to and environmental release of recombinant organisms. Each institution (e.g., university, hospital or commercial laboratory) is responsible for conducting rDNA research safely and in compliance with the NIHG. This is accomplished through an administrative system which defines responsibilities and requires comprehensive risk assessments by knowledgeable scientists and biosafety officers, implementation of exposure controls, medical surveillance programmes and emergency planning. An Institutional Biosafety Committee (IBC) provides the mechanisms for experiment review and approval within the institution. In some cases, approval of NIH Recombinant Advisory Committee (RAC) itself is required.

 

The degree of control depends on the severity of the risk and is described in terms of Biosafety Level (BL) designations 1-4; BL1 being the least restrictive and BL4 the most. Containment guidelines are given for research, large scale (greater than 10 litres of culture) R&D, large scale production and animal and plant experiments at both large and small scale.

 

Appendix G of the NIHG (NIH 1996) describes physical containment at the laboratory scale. BL1 is appropriate for work with agents of no known or of minimal potential hazard to laboratory personnel or the environment. The laboratory is not separated from the general traffic patterns in the building. Work is conducted on the open benchtops. No special containment devices are required or used. Laboratory personnel are trained in laboratory procedures and supervised by a scientist with general training in microbiology or a related science.

 

BL2 is suitable for work involving agents of moderate potential hazard to personnel and the environment. Access to the laboratory is limited when work is being conducted, workers have specific training in handling pathogenic agents and are directed by competent scientists, and work which creates aerosols is conducted in biological safety cabinets or other containment equipment. This work may require medical surveillance or vaccinations as appropriate and determined by the IBC.

 

BL3 is applicable when work is conducted with indigenous or exotic agents which may cause serious or potentially lethal disease as a result of exposure by inhalation. Workers have specific training and are supervised by competent scientists who are experienced in working with handling these hazardous agents. All procedures are done under containment conditions requiring special engineering and PPE.

 

BL4 is reserved for the most dangerous and exotic agents that pose a high individual and community risk of life-threatening disease. There are only a few BL4 laboratories in the world.

 

Appendix K addresses physical containment for research or production activities in volumes greater than 10 l (large scale). As in the small-scale guidelines, there is a hierarchy of containment requirements from lowest to highest hazard potential: GLSP to BL3-Large-Scale (BL3-LS).

 

The NIHG, Appendix P, covers work with plants at bench level, growth chamber and greenhouse scale. As the introduction notes: “The principal purpose of plant containment is to avoid the unintentional transmission of a recombinant DNA-containing plant genome, including nuclear or organelle hereditary material or release of recombinant DNA derived organisms associated with plants. In general these organisms pose no threat to human health or higher animals, unless deliberately modified for that purpose. However, the inadvertent spread of a serious pathogen from a greenhouse to a local agricultural crop or the unintentional introduction and establishment of an organism in a new ecosystem is possible” (NIH 1996). In the United States, the EPA and the USDA’s Animal and Plant Health Inspection Service (APHIS) are jointly responsible for risk assessment and for reviewing the data generated prior to giving approval for field release testing (EPA 1996; Foudin and Gay 1995). Issues such as persistence and spread in water, air and soil, by insect and animal species, the presence of other similar crops in the area, environmental stability (frost or heat sensitivity) and competition with native species are evaluated-often first in the greenhouse (Liberman et al. 1996).

 

Plant containment levels for facilities and practices also range from BL1 to BL4. Typical BL1 experiments involve self-cloning. BL2 may involve transfer of traits from a pathogen to a host plant. BL3 might involve toxin expression or environmentally hazardous agents. Worker protection is achieved in the various levels by PPE and engineering controls such as greenhouses and headhouses with directional airflow and high efficiency particulate air filters (HEPA) to prevent pollen release. Depending on the risk, environmental and community protection from potentially hazardous agents can be achieved by biological controls. Examples are a temperature sensitive trait, drug sensitivity trait or nutritional requirement not present in nature.

 

As scientific knowledge increased and technology advanced, it was expected that the NIHG would need review and revision. Over the last 20 years, the RAC has met to consider and approve proposals for changes. For example, the NIHG no longer issue blanket prohibitions on deliberate release of genetically engineered organisms; agricultural products field trial releases and human gene therapy experiments are allowed in appropriate circumstances and after suitable risk assessment. One very significant amendment to the NIHG was the creation of the GLSP containment category. It relaxed the containment requirements for “non-pathogenic, non-toxigenic recombinant strains derived from host organisms that have an extended history of safe large scale use, or which have built in environmental limitations that permit optimum growth in the large scale setting but limited survival without adverse consequences in the environment” (NIH 1991). This mechanism has allowed the technology to progress while still considering safety needs.

 

Controls: The European Community Example

In April 1990 the European Community (EC) enacted two Directives on the contained use and deliberate release into the environment of GMOs. Both Directives require Member States to ensure that all appropriate measures are taken to avoid adverse effects on human health or the environment, in particular by making the user assess all relevant risks in advance. In Germany, the Genetic Technology Act was passed in 1990 partially in response to the EC Directives, but also to respond to a need for legal authority to construct a trial operation recombinant insulin production facility (Reutsch and Broderick 1996). In Switzerland, the regulations are based on the US NIHG, Council directives of the EC and the German law on gene technology. The Swiss require annual registration and updates of experiments to the government. In general, the rDNA standards in Europe are more restrictive than in the US, and this has contributed to many European pharmaceutical firms moving rDNA research from their home countries. However, the Swiss regulations allow a Large Scale Safety Level 4 category, which is not permitted under the NIHG (SCBS 1995).

 

Products of Biotechnology

Some of the biological and pharmaceutical products which have been successfully made by recombinant DNA biotechnologies include: human insulin; human growth hormone; hepatitis vaccines; alpha-interferon; beta-interferon; gamma-interferon; Granulocyte colony stimulating factor; tissue plasminogen activator; Granulocyte-macrophage colony stimulating factor; IL2; Erythropoietin; Crymax, an insecticide product for the control of caterpillars in vegetable; tree nut and vine crops; Flavr Savr (TM) tomato; Chymogen, an enzyme that makes cheese; ATIII (antithrombin III), derived from transgenic goat milk used to prevent blood clots in surgery; BST and PST (bovine and porcine somatotropin) used to boost milk and meat production.

 

Health Problems and Disease Patterns

There are five main health hazards from exposure to microorganisms or their products in industrial scale biotechnology:

 

· infection

· reaction to endotoxin

· allergy to the microorganisms

· allergic reaction to a product

· toxic reaction to a product.

 

Infection is unlikely since non-pathogens are used in most industrial processes. However, it is possible that microorganisms considered to be harmless such as Pseudomonas and Aspergillus species may cause infection in immunocompromised individuals (Bennett 1990). Exposure to endotoxin, a component of the lippopolysaccharide layer of the cell wall of all gram negative bacteria, at concentrations greater than about 300 ng/m3 causes transient flu-like symptoms (Balzer 1994). Workers in many industries including traditional agriculture and biotechnology have experienced the effects of endotoxin exposure. Allergic reactions to the microorganism or product also occur in many industries. Occupational asthma has been diagnosed in the biotechnology industry for a wide range of microorganisms and products including Aspergillus niger, Penicillium spp. and proteases; some companies have noted incidences in greater than 12% of the workforce. Toxic reactions can be as varied as the organisms and products. Exposure to antibiotics has been shown to cause shifts in microbial flora in the gut. Fungi are known to be capable of producing toxins and carcinogens under certain growth conditions (Bennett 1990).

 

To address concern that exposed workers would be the first to develop any potential adverse health effects from the new technology, medical surveillance of rDNA workers has been a part of the NIHG since their beginning. Institutional Biosafety Committees, in consultation with the occupational health physician, are charged with determining, on a project by project basis, what medical surveillance is appropriate. Depending on the identity of the specific agent, the nature of the biological hazard, the potential routes of exposure and availability of vaccines, the components of the medical surveillance programme might include pre-placement physical, periodic follow-up exams, specific vaccines, specific allergy and illness evaluations, pre-exposure sera and epidemiological surveys.

 

Bennett (1990) believes it is unlikely that genetically modified microorganisms will pose more of an infection or allergic risk than the original organism, but there could be additional risks from the novel product, or the rDNA. A recent report notes the expression of a brazil-nut allergen in transgenic soybeans may cause unexpected health effects among workers and consumers (Nordlee et al. 1996). Other novel hazards could be the use of animal cell lines containing unknown or undetected oncogenes or viruses potentially harmful to humans.

 

It is important to note the early fears concerning the creation of genetically dangerous mutant species or super-toxins have not materialized. The WHO found that biotechnology poses no risks that are different from other processing industries (Miller 1983), and, according to Liberman, Ducatman and Fink (1990), “the current consensus is that the potential risks of rDNA were overstated initially and that the hazards associated with this research are similar to those associated with the organism, vector, DNA, solvents and physical apparatus being used”. They conclude that engineered organisms are bound to have hazards; however, containment can be defined to minimize exposure.

 

It is very difficult to identify occupational exposures specific to the biotechnology industry. “Biotechnology” is not a separate industry with a distinguishing Standard Industrial Classification (SIC) code; rather, it is viewed as a process or set of tools used in many industrial applications. Consequently, when accidents and exposures are reported, the data on cases involving biotechnology workers are included among data on all others which occur in the host industry sector (e.g., agriculture, pharmaceutical industry or health care). Furthermore, laboratory incidents and accidents are known to be under reported.

 

Few illnesses specifically due to genetically altered DNA have been reported; however, they are not unknown. At least one documented local infection and seroconversion was reported when a worker suffered a needle stick contaminated with a recombinant vaccinia vector (Openshaw et al. 1991).

 

Policy Issues

In the 1980s the first products of biotechnology emerged in the US and Europe. Genetically engineered insulin was approved for use in 1982, as was a genetically engineered vaccine against the pig disease “scours” (Sattelle 1991). Recombinant bovine somatotropin (BST) has been shown to increase a cow’s milk production and the weight of beef cattle. Concerns were raised about public health and product safety and whether existing regulations were adequate to address these concerns in all the different areas where products of biotechnology could be marketed. The NIHG provide protection of workers and the environment during research and development stages. Product safety and efficacy is not a NIHG responsibility. In the US, through the Coordinated Framework, potential risks of the products of biotechnology are evaluated by the most appropriate agency (FDA, EPA or USDA).

 

The debate over safety of genetic engineering and the products of biotechnology continues (Thomas and Myers 1993), especially with respect to agricultural applications and foods for human consumption. Consumers in some areas want produce labelled to identify which are the traditional hybrids and which are derived from biotechnology. Certain manufacturers of dairy products refuse to use milk from cows receiving BST. It is banned in some countries (e.g., Switzerland). The FDA has deemed the products to be safe, but there are also economic and social issues which may not be acceptable to the public. BST may indeed create a competitive disadvantage for smaller farms, most of which are family run. Unlike medical applications where there may be no alternative to genetically engineered treatment, when traditional foods are available and plentiful, the public is in favour of traditional hybridization over recombinant food. However, harsh environments and the current worldwide food shortage may change this attitude.

 

Newer applications of the technology to human health and inherited diseases have revived the concerns and created new ethical and social issues. The Human Genome Project, which began in the early 1980s, will produce a physical and genetic map of human genetic material. This map will provide researchers with information to compare “healthy or normal” and “diseased” gene expression to better understand, predict and point to cures for the basic genetic defects. Human Genome technologies have produced new diagnostic tests for Huntington’s Disease, cystic fibrosis and breast and colon cancers. Somatic human gene therapy is expected to correct or improve treatments for inherited diseases. DNA “fingerprinting” by restriction fragment polymorphism mapping of genetic material is used as forensic evidence in cases of rape, kidnapping and homicide. It can be used to prove (or, technically, disprove) paternity. It can also be used in more controversial areas, such as for assessing chances of developing cancer and heart disease for insurance coverage and preventative treatments or as evidence in war crimes tribunals and as genetic “dogtags” in the military.

 

Though technically feasible, work on human germ-line experiments (transmissible from generation to generation) have not been considered for approval in the US due to the serious social and ethical considerations. However, public hearings are planned in the US to reopen the discussion of human germ-line therapy and the desirable trait enhancements not associated with diseases.

 

Finally, in addition to safety, social and ethical issues, legal theories about ownership of genes and DNA and liability for use or misuse are still evolving.

 

Long-term implications of environmental release of various agents need to be followed. New biological containment and host range issues will come up for work which is carefully and appropriately controlled in the laboratory environment, but for which all environmental possibilities are not known. Developing countries, where adequate scientific expertise and or regulatory agencies may not exist, may find themselves either unwilling or unable to take on the assessment of risk for their particular environment. This could lead to unnecessary restrictions or an imprudent “open-door” policy, either of which could prove damaging to the long-term benefit of the country (Ho 1996).

 

In addition, caution is important when introducing engineered agricultural agents into novel environments where frost or other natural containment pressures are not present. Will indigenous populations or natural exchangers of genetic information mate with recombinant agents in the wild resulting in transfer of engineered traits? Would these traits prove harmful in other agents? What would be the effect to the treatment administrators? Will immune reactions limit spread? Are engineered live agents capable of crossing species barriers? Do they persist in the environment of deserts, mountains, plain and cities?

 

Summary

Modern biotechnology in the United States has developed under consensus guidelines and local ordinance since the early 1970s. Careful scrutiny has shown no unexpected, uncontrollable traits expressed by a recombinant organism. It is a useful technology, without which many medical improvements based on natural therapeutic proteins would not have been possible. In many developed countries biotechnology is a major economic force and an entire industry has grown around the biotechnology revolution.

 

Medical issues for biotechnology workers are related to the specific host, vector and DNA risks and the physical operations performed. So far worker illness has been preventable by engineering, work practice, vaccines and biological containment controls specific to the risk as assessed on a case by case basis. And the administrative structure is in place to do prospective risk assessments for each new experimental protocol. Whether this safety track record continues into the environmental release of viable materials arena is a matter of continued evaluation of the potential environmental risks-persistence, spread, natural exchangers, characteristics of the host cell, host range specificity for transfer agents used, nature of the inserted gene and so on. This is important to consider for all possible environments and species affected in order to minimize surprises that nature often presents.