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  • Decoding "Coding": Information and DNA Author(s): Sahotra Sarkar Source: BioScience, Vol. 46, No. 11 (Dec., 1996), pp. 857-864 Published by: University of California Press on behalf of the American Institute of Biological Sciences Stable URL: . Accessed: 16/10/2013 09:58

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  • Thinking of Biology

    Decoding "coding"-information and DNA

    Most biologists would prob- ably be more bored by than surprised at, and certainly

    not impressed by the originality of, the claim that the central core of the conceptual structure of contempo- rary molecular biology can be en- capsulated in the following three precepts:

    * All hereditary information resides in the DNA sequences of organisms. * This information is transferred from DNA to RNA through the pro- cess of transcription, and from RNA to protein through translation. * This information is never trans- ferred from protein to nucleic acid sequences.

    Following Crick (1958), the last pre- cept is usually called the "Central Dogma" of molecular biology.

    These three precepts are so uni- versally accepted that they usually find their way into introductory bi- ology texts. Nevertheless, they are at best misleading, and at worst sim- ply vacuous, in the sense that they can play no significant explanatory role in molecular biology. The rea- son for this is that there is no clear technical notion of "information" in molecular biology. "Information" is little more than a metaphor that masquerades as a technical concept and leads to a misleading picture of the conceptual structure of molecu- lar biology. Metaphors are ubiqui- tous in science. When they provide succinct or easily comprehensible accounts of complex technical con- cepts, they are particularly useful for communicative or didactic pur- poses. However, when they serve only as surrogates for nonexistent technical concepts, their influence is less than benign. In molecular biol-

    ogy, "information" and associated terms (especially "coding") belong to the latter class of metaphors. This claim is, no doubt, a bold one-to develop the arguments in its favor requires an excursion into the his- tory of molecular biology, a discus- sion of how the term "information" came to be introduced, and why, for all its initial plausibility as a useful theoretical concept, there is little to recommend its continued use today.

    Information and molecular biology Historically, the term "information" entered molecular biology as part of a putative theory of biological speci- ficity. By around 1930, it had be- come clear that molecular interac- tions in living organisms are highly specific in the sense that particular molecules interact with exactly one, or at most a few, reagents. Enzymes act on specific substrates. Living organisms produce antibodies that are highly specific, not only to natu- rally occurring antigens, but also to artificial antigens (Landsteiner 1936). Even the action of genes was sometimes described using "speci- ficity": genes specified precise phe- notypes to different degrees of accu- racy called their "specificity" (Timof6eff-Ressovsky and Timof6eff- Ressovsky 1926). In genetics, the ultimate exemplar of specificity be- came the gene-enzyme relationship (Beadle and Tatum 1941): "one gene-one enzyme" was perhaps the most important organizing hypoth- esis of early molecular biology.

    By the end of the 1930s, a highly successful theory of specificity (and one that remains central to molecu- lar biology) emerged. Due primarily to Linus Pauling (e.g., Pauling 1940), although with many antecedents, this theory claimed that the behavior of a macromolecule is determined by

    its conformation, and that what mediates biological interactions is a precise lock-and-key fit between the shapes of molecules. In the 1940s, when no three-dimensional struc- ture of a biological macromolecule had yet been determined, the con- formational theory of specificity was speculative. The demonstration of its approximate truth for a wide variety of interactions, which came in the late 1950s and 1960s, was one of molecular biology's most signifi- cant triumphs. Just as "one gene- one enzyme" was the archetypal slo- gan of early molecular biology, "structure determines function" came to be the dominating principle of the field during its triumphant 1960s.

    Meanwhile, back in 1944, in What Is Life?, Erwin Schrodinger had in- troduced a conceptual scheme that raised the possibility of a startlingly different source of specificity. Schrodinger asked how so tiny an object as the nucleus of a fertilized cell could contain all of the specifi- cations (i.e., instructions) necessary for normal development of an adult organism. He stated that there ex- isted in the nucleus some structure whose organization was interpreted as "an elaborate code-script," which he compared to the Morse code

    (Schr6dinger 1944). Although he was willing to countenance codes in more than one dimension, even a linear code based on a 5-letter alphabet and word of up to 25 letters could generate more than 1017 patterns. Thus the arrangement of the units rather than their physical shape be- came the source of specificity in Schrodinger's model. In the postwar era, when many scientists who were initially trained in physics turned their attention to biology for the first time, What Is Life? was influen- tial in setting the agenda of a new biology (Sarkar 1991). by Sahotra Sarkar

    December 1996 857

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  • The 1940s also saw an explosive growth of microbial genetics, start- ing with Luria and Delbriick's (1943) demonstration of spontaneous mu- tagenesis in bacteria; continuing, especially, with Avery and col- leagues' (1944) demonstration of DNA as the likely genetic material; and culminating with Joshua Lederberg's discovery of recombi- nation in bacteria (Lederberg and Tatum 1946a, b). "Transformation," "induction," and "transduction" were some of the new terms intro- duced to describe these phenomena (Ephrussi et al. 1953). In an attempt to navigate through this termino- logical morass, Ephrussi et al. (1953) suggested that the term "inter- bacterial information" replace them all. This was the first modern use of "information" in genetics. Ephrussi et al. (1953, p. 701) emphasized that the use of this term "does not neces- sarily imply the transfer of material substances, and [that they] recog- nize the possible future importance of cybernetics at the bacterial level."

    Immediately after the publication of Ephrussi et al. (1953)-in fact, in the next issue of Nature-Watson and Crick (1953a) published the double helix model of DNA. The base pairing-A:T and C:G-that they proposed showed a possible way in which the specificities between the two helices could be involved in the formation of exact replicas. Moreover, in their second paper on the model (Watson and Crick 1953b, p. 964), they went on to use "infor- mation" explicitly, and defined it

    implicitly as what the "code" car- ried: "The phosphate-sugar back- bone in our model is completely regular but any sequence of the pairs of bases can fit into the structure. It follows that in a long molecule many different permutations are possible, and it therefore seems likely that the precise sequence of bases is the code which carries the genetic informa- tion."

    "Information" was finally defined explicitly by Crick in 1958, who identified it with the specification of a protein sequence. Crick's (1958) concern was the synthesis of pro- teins. There were three separate fac- tors involved, he argued: "the flow of energy, the flow of matter, and the flow of information" (Crick

    1958). The former two exhausted the physics and chemistry of the situation, whereas information was peculiar to biological systems. Crick (1958, p. 144) defined "informa- tion" with more care than ever be- fore in this context: "By information I mean the specification of the amino acid sequence of the protein." He took it for granted that the genetic information was encoded in a DNA sequence. The physics and chemis- try of folding of a protein, Crick hypothesized, were purely a result of its amino acid sequence. This is the well-known "sequence hypoth- esis" (which remains unproved be- cause of the continued insolvability of


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