LifeSeq

Human Gene Expression and Sequence Database

LifeSeq¨ database is one of the world's largest sources of genomic data. This commercial database of human gene expression and sequence information is used daily by scientists at more than 50 pharmaceutical research and development sites worldwide to identify therapeutic targets, to develop new approaches for diagnosing disease, and to understand the pharmacological and toxicological impact of new drugs on human tissues. LifeSeq software is a relational database containing gene expression information for hundreds of different cells and tissues, in both normal and diseased systems, and at different developmental stages. The rapidly growing database is compiled from Incyte's proprietary high-throughput cDNA sequencing and bioanalysis. It currently contains over 3 million cDNA sequences (ESTs), more than 2.3 million of them Incyte-proprietary. This represents an estimated 100,000 to 120,000 distinct human genes, the majority of which are not available in the public domain.

LifeSeq Atlas

../de_codifications/technique_tech-nology.html

This cross-disciplinary engagement with the notion of "information" was, still, only a partial investment in the way that information theory and cybernetics had defined information during the 1950s. During the same period, Claude Shannon and Warren Weaver, working at Bell Research Labs, developed their "mathematical theory of information," which was primarily dependent on regarding information as a discrete quantity of signals (whether textual, electronic, digital, or even musical) independent of the quality or content of those signals. As Weaver pointed out:
The word information, in this theory, is used in a special sense that must not be confused with its ordinary usage. In particular, information must not be confused with meaning. In fact, two messages, one of which is heavily loaded with meaning and the other which is pure nonsense, can be exactly equivalent, from the present viewpoint, as regards information.

For Shannon and Weaver, information was a pattern, a particular organization in an inverse relationship to entropy, or the tendency of systems to degrade or become disorganized over time. Though Norbert Wiener's notion of information in cybernetics (the study of communication and control in systems - machinic or organismic - based on feedback) contains some differences from that of Shannon and Weaver, Wiener too discusses information as "negative entropy." Information theory was likewise conceived of as the "fundamental problem of communication," which was concerned with "reproducing at one point either exactly or approximately a message selected at another point"(31). In terms of Shannon's research for Bell Labs, and as an important contribution to network-based research that led to the development of the Internet, information theory attempted to map out the highest possible statistical rate of successful transmission with the lowest possibility for unwanted or excess information, termed "noise." Given this perspective, Watson and Crick's usage of information with regards to DNA was primarily a metaphorical appropriation, as Evelyn Fox Keller points out. In contrast to information theory, the content or "meaning" of a particular DNA sequence was highly important for geneticists; a single point mutation or alteration in the genetic code would significantly affect a wide range of biochemical properties in the organism. Though all of this concerns an emerging paradigm of viewing organisms, machines, and other complex relationships in terms of communication and information processing systems, the apparent intersection of information sciences and molecular biology contained some important differences. Watson and Crick's model differed, then, on the defining properties of what constituted information, as well as the mechanics of information as a process (linear transmission as opposed to cybernetics' feedback loops).

However, with the emergence of new techniques and technologies in genetics and biotechnology research (beginning with the development of recombinant DNA in the 1970s) the relationship between genetics and informatics becomes a much more intimate, almost inter-disciplinary instance where the conceptual node of "information" is continually re-negotiated. A few brief examples:

Recombinant DNA: In 1973 American geneticists Herbert Boyer and Stanley Cohen performed the first successful transmission of a gene between two different organisms. Their experiments made use of two types of enzymes naturally occurring in microorganisms, restriction enzymes and ligase enzymes, which, respectively, perform the cutting and stitching procedures of molecules within a DNA sequence. Using restriction enzymes, they isolated a gene for an antibiotic resistance and used the same restriction enzyme on DNA from an African clawed toad. They found that the restriction enzyme EcoR1 not only cleaved DNA at a specific site, but also synthesized the sticky ends required for the ligase procedure. After combining these fragments into the first recombinant use of a plasmid (bacteria, they used these bacterial cells to reproduce this recombinant gene. Cohen dubbed the replicating plasmid containing the spliced gene a "chimera," and coined the term "recombinant DNA" to describe their technique of gene splicing. In 1980 they were granted a patent (applied for in 1974, the Stanley Cohen-Herbert Boyer patent) for the technique of gene splicing.

Polymerase Chain Reaction (PCR): In the mid-1980s, a group of researchers working at the biotech startup company Cetus developed a technological methodology for the large-scale, automated production and analysis of DNA sequences. Called Polymerase Chain Reaction, this technology applied a series of heating and cooling cycles to a specified region of DNA. The heating cycle would weaken and break the bonds holding the double-stranded DNA molecule, at which time "primers" (beginning and ending molecules used for tagging specific sites on a DNA sequence) were added, followed by a Polymerase enzyme, which proceed to synthesize complementary strands as the cooling cycle was initiated, forming two double-stranded DNA molecules from a single one. Once this procedure is repeated, the amount of the desired DNA sequence is exponentially amplified, making abundant "raw material" available for research. PCR was one of among many technique-technology hybrids which helped to contribute to the biotechnology boom of the 1980s, and in 1993 Kary Mullis was awarded the Nobel Prize in chemistry for his involvement with the development of PCR.

In terms of genetic information, the development of recombinant DNA techniques actually involves two distinct procedures. The first is that of intentionally (that is, as opposed to naturally-occurring mutations in the genetic sequence) re-organizing DNA, either by producing transgenic types of organisms (a gene or genetic sequence transferred from one organism to another, as Cohen and Boyer did), or by introducing specially engineered sequences (DNA or RNA altered or prepared outside the organism) into the genetic sequence of an organism. The second procedure relates to the way in which the recombinant genetic sequence is or is not successfully integrated into the organism's overall molecular and biochemical makeup. Sometimes this is accomplished through cell replication normally occurring in the organism, but often is done through cloning techniques, such as the use of plasmids to effectively mass-produce the recombinant sequence before being introduced into the organism.

As Paul Rabinow mentions, the invention of PCR not only changed and challenged genetics and biotechnology research, but it also constitutes a redefinition of how the organism is approached on the molecular level:
Genes were becoming manipulable biochemical matter. Khorana [a well-known researcher in genetic cloning] was trying to harness a biological process (polymerization) as part of a larger project to make an artificial version of a biological unit, a gene. Mullis's decontextualization and exponential amplification was the opposite of Khorana's efforts at the mimicry of nature. Mullis discovered a way to turn a biological process (polymerization) into a machine; nature served (bio)mechanics.
Though the polarization of nature/culture in Rabinow's account might be nuanced, the relationship between the genetic engineering experiments of the 1970s and the development of PCR in the 1980s is significant. Much of genetic engineering (including recombinant DNA techniques, genetic cloning, and the use of restriction enzymes for cutting, ligases for stitching, and reverse transcriptases for the reverse production of DNA from RNA) had to do with the harnessing and concerted redirecting of "naturally occurring" biochemical processes at the molecular level. For example, restriction enzymes are often found as components of the immune system, identifying and attaching themselves to foreign elements (antigens) to be destroyed. The precision and specificity of restriction enzymes made them ideal tools for identifying, marking, and cutting at particular regions along the DNA molecule, making them one of the major tools for genetic engineering.

By contrast, PCR, in one sense, had nothing at all to do with genetics or biotechnology; it is, first of all, a little black box, a technological object designed for a specific (research-based, industrial, commercial) purpose. In another sense, though, it is a technology which develops concurrently with and which is specific to genetics and biotechnology research, and in this sense PCR technology follows upon the developments of other genetics/biotechnology-related machines available to laboratories during the 70s and 80s, such as spectrophotometers (often used for recognizing strong or denatured bonds in molecules) and DNA synthesizers (which automate the replicating and transcription processes utilized by genetic engineers). The fact that bio-technologies such as PCR produce biological components outside of an organic or organismic context, and that PCR applies computer-based technologies (such as "loop" programs designed to carry out repetitive tasks) towards processes not found in the organism, both suggest that a specific type of cyborgic or technoscientific relationship is being produced within the discourses and research of molecular biology.

A genetically-engineered sequence of DNA (say, one coding for the production of a particular protein needed by the immune system), produced in a DNA synthesizer, "tagged" by radioactive molecular markers (so that researchers can follow the progress of the engineered sequence's integration into the organism), amplified by PCR, then introduced into the genetic sequence of an organism - this is indeed a highly complex instance of the integration of machine and organism (or, better, of machinic and organismic logics) which Wiener emphasized as one of the primary focal points of his science of cybernetics during the post-war period.