Assessing physical containment in recombinant DNA facilities. 1984

E Fisher, and D R Lincoln

This paper has presented a computer model that has been developed to explore the effectiveness of various physical containment strategies. The specific applications that are considered here concern recombinant DNA operations, a technology where technical constraints inhibit the direct monitoring of physical containment effectiveness. Simulations have been used to assess several aspects of recombinant DNA containment, including the effects of using different protocols and host organisms, establishing tradeoffs between physical and biological containment levels, and recognizing the variability introduced by human error and equipment failures. In considering these questions, we have focused on the operator's exposure, although the model that has been developed can also be used to estimate the total release of viable recombinant organisms to the environment. Comparing benchtop protocol simulation results with scale-up protocol results indicates that operator exposure in the former situation may be two or three orders of magnitude lower. A similar difference is apparent between the operator's exposure during a standard scale-up protocol and a protocol that replaces manual sampling with automated sampling. Because the specific activities in a facility influence organism release dramatically, physical containment effectiveness cannot be represented with a single estimate of organisms released per facility per time for each containment level. Results from simulations using E. coli chi 1776 and simulations using hardier organisms indicate that, in a well ventilated facility, the operator's inhalation of viable organisms is essentially unaffected by using the disabled host organism. It should be noted, however, that these simulation results only reflect the differences in the survival of the aerosolized organisms; the relative survival and establishment of organisms after inhalation is not considered.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008962 Models, Theoretical Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Experimental Model,Experimental Models,Mathematical Model,Model, Experimental,Models (Theoretical),Models, Experimental,Models, Theoretic,Theoretical Study,Mathematical Models,Model (Theoretical),Model, Mathematical,Model, Theoretical,Models, Mathematical,Studies, Theoretical,Study, Theoretical,Theoretical Model,Theoretical Models,Theoretical Studies
D003201 Computers Programmable electronic devices designed to accept data, perform prescribed mathematical and logical operations at high speed, and display the results of these operations. Calculators, Programmable,Computer Hardware,Computers, Digital,Hardware, Computer,Calculator, Programmable,Computer,Computer, Digital,Digital Computer,Digital Computers,Programmable Calculator,Programmable Calculators
D003264 Containment of Biohazards Physical and biological barriers to the spread of potentially hazardous biologically active agents such as bacteria, viruses, recombinant nucleotides, or contaminated bio-specimens. Biohazards Containment,Biohazard Containment,Biological Containment,Biosafety,Containment, Biologic,Physical Containment,Biologic Containment,Containment, Biohazard,Containment, Biohazards,Containment, Biological,Containment, Physical
D004274 DNA, Recombinant Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected. Genes, Spliced,Recombinant DNA,Spliced Gene,Recombinant DNA Research,Recombination Joint,DNA Research, Recombinant,Gene, Spliced,Joint, Recombination,Research, Recombinant DNA,Spliced Genes
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D005822 Genetic Vectors DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition. Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D014691 Ventilation Supplying a building or house, their rooms and corridors, with fresh air. The controlling of the environment thus may be in public or domestic sites and in medical or non-medical locales. (From Dorland, 28th ed) Ventilations

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