April Smith

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721.

English metaphysical poetry, from Donne to Marvell, is conspicuously witty. A. J. Smith seeks the central importance of wit in the thinking of the metaphysical poets, and argues that metaphysical wit is essentially different from other modes of wit current in Renaissance Europe. Formal theories and rhetorics of wit are considered both for their theoretical import and their appraisals of wit in practice. Prevailing fashions of witty invention are scrutinized in Italian, French, and Spanish writings, so as to bring out the nature and effect of various forms of wit: conceited, hieroglyphic, transformational, and others from which the metaphysical mode is distinguished. He locates the basis of Renaissance wit in the received conception of the created order and a theory of literary innovation inherent in Humanist belief, which led to novel couplings of time and eternity, body and soul, man and God. Yet, he finds that metaphysical wit distinctively works to discover a spiritual presence in sensible events; and he traces its demise in the 1660s to changes in the understanding of the natural world associated with the rise of empirical science.

In her careful consideration of my book, The Problem of Perception, Susanna Siegel highlights what she takes to be a number of shortcomings in the work. First, she suggests that a sense-datum theorist has two options—what she calls the “complex sense-data option” and the “two-factor option”—that survive the argument of my book unscathed. I consider these two options in the first two sections of this reply. Secondly, she criticizes my suggestion that there are three and only three basic and independent sources of perceptual consciousness: an issue I take up in my third section. Thirdly, she expresses reservations about my response to the argument from hallucination. In particular, she argues that the phenomenological considerations on which I put so much weight cannot settle the fundamental issue here. I address this criticism in the fourth section of this reply. Finally, she spends a certain amount of time discussing the notion of a “veridicality-relevant property”, a topic to which I devote the concluding section of this reply.