Bruce R. Levin

The kinetics of conjugative plasmid transmission: Fit of a simple mass action model

Abstract A mass action model for the infectious transmission of conjugative plasmids and procedures to estimate its parameters are presented. The suitability of this model as an analog of the kinetics of conjugative plasmid transmission is examined with batch and chemostat populations of Escherichia coli K-12 and three of its plasmids, F-lac-pro, R1 (Km-Cm-Ap), and R1-drd-19 (Km-Cm-Ap). Evidence is presented that this mass action model, with a unique and constant rate parameter, represents a reasonable analog of the kinetics of plasmid transfer for bacterial populations dividing at a constant rate in either exponentially growing cultures or at equilibrium in chemostats. As anticipated from this model magnitudes of the transfer rate constant for these plasmids appear to be relatively insensitive to both total cell density and the donor-recipient ratio. For all plasmids, the value of the transfer rate constant in rapidly dividing (exponentially growing) cultures is considerably greater than its corresponding value in slowly dividing, chemostat equilibrium cultures and the values of the transfer rate constant of the permanently derepressed plasmids F-lac-pro and R1-drd-19 are considerably greater than that of the wild-type, repressed transfer plasmid R1. The implications of this apparent fit to a mass action model are discussed and a recommendation is made to use the transfer rate constant as the measure of the fertility of conjugative plasmids.

Evaluating the risk of releasing genetically engineered organisms

Abstract This article considers the question of a priori assessment of the safety of releasing recombinant DNA engineered organisms. Now and for the foreseeable future, decisions to release such an organism must be based on the results of limited, case-by-case risk assessment studies. The criteria calling for the termination of release programs must be agreed upon in advance of these studies. There is no justification for excluding classes of release organisms from risk assessment. Theory is useful in suggesting a hierarchy of risks, raising the questions that have to be addressed in case-by-case risk assessment and providing protocols for the standardization and execution of these studies. We do not believe that theory can be used to argue categorically for or against the safety of specific releases of recombinant DNA engineered organisms.

A quantitative model suggests immune memory involves the colocalization of B and Th cells.

A prominent and essential feature of the humoral immune response of vertebrates is immunologic memory: the ability to recall previous exposure to antigen. We present a mathematical model of the growth and interactions of the major cell populations involved in the humoral immune response. Our analysis of this model predicts that the formation of a dynamic association between small numbers of antigen-specific B and Th cells, colocalization, is sufficient to account for memory and the kinetics of the secondary response--neither specifically differentiated Th or B memory cells nor networks of antigen and anti-idiotypes are required. The colocalization hypothesis explains a number of existing experimental observations and can be tested by straightforward experiments which we describe.

Microbial Ecology and Population Biology

In their roles as decomposers, recyclers, pathogens, extractors and synthesizers, bacteria are responsible for maintaining the flow of nutrients through ecological communities, regulating the densities of populations in those communities and preventing the build-up of organic matter and toxic compounds. Microbial ecology and population biology study bacteria in these different roles and the factors affecting the distribution, abundance and evolution of populations of these microorganisms and their genetic parasites, plasmids, phage and transposons. I describe and critically consider three ways by which microbial ecology and population biology contribute to the quest for solutions to environmental problems; i) measuring and monitoring the effects of insults to the environment; ii) elucidating the factors responsible for maintaining the integrity of undisturbed ecological communities; and iii) identifying and developing microbes to degrade and recycle wastes, detoxify pollutants, as alternatives to noxious pesticides and as producers of useful compounds. 1 follow this broad excursion into the contribution of my field with a more personal consideration, confessions of an academic microbial population biologist. I conclude with a couple of caveats (musings); the liability of relying solely on technical solutions to environmental problems, and the effects of the separation of academic and applied biology on the quest for these solutions.