Irina Grigorjan
Vsevolod Makeev ::: Biography

BIOCHIPS AND INDUSTRIAL BIOLOGY

A living cell is very complex and its activity involves many interacting systems. The control of cell operation is mainly performed by genes, segments of the DNA molecule that store information about the construction of other molecules, which participate in different life processes. A gene works when this information is retrieved.
Biologists and physicians need to know how huge cascades of interacting and mutually controlling genes respond at some change in external conditions, for instance when a drug is taken.
The total number of genes is measured in thousands, from 6200 for yeast to approximately 38000 for humans. A principal living process is usually regulated by hundreds of genes. Until recently, it was almost impossible to obtain, store, and process such quantities of data. The progress of the computer industry led to the development of new technologies that allow one to simultaneously obtain experimental information on operation of many genes in a cell, and to process this information leading to a simple and reliable conclusion such as a medical diagnosis.

This on-line version of the book "Biomediale. Contemporary Society and Genomic Culture" is not full. The unabridged edition can be purchased in printed form as anthology. Requests should be sent to: bulatov@ncca.koenig.ru (full information) or in written form: 236000, Russia, Kaliningrad, 18, Marx str., The National Publishing House “Yantarny Skaz”. Phone requests: Kaliningrad +7(0112)216251, Saint-Petersburg +7(812)3885881, Moscow +7(095)2867666. On-line bookshop (in Russian): http://www.yantskaz.ru. Full reference to this book: "Biomediale. Contemporary Society and Genomic Culture". Edited and curated by Dmitry Bulatov. The National Centre for Contemporary art (Kaliningrad branch, Russia), The National Publishing House “Yantarny Skaz”: Kaliningrad, 2004. ISBN 5-7406-0853-7

The cDNA-based biochips are the most popular, they became a breakthrough technology in biomedical science. Thus we now enlarge on the subject of how they are prepared, how they are used to obtain data, and how the data are processed. The principal technology here is the usage of a glass surface to which the genetic material is applied; this allows one to use minor quantities of the substance under test, and to locate with high precision the particular cDNA type at the array. Robots similar to those used in microelectronics for chip production can also be employed for biochip preparation. (Fig. 1) Molecules of each DNA type are prepared in many identical copies with the help of a process called amplification, this process can also be automated. After amplification, the genetic material is applied to a given point on the glass surface (colloquially known as "printing"), and then is chemically bonded to the glass (immobilization). A special treatment of the glass surface is necessary before immobilization and the printed biochip should be treated with UV stimulated chemical bonding between the DNA molecules and the glass. (Fig. 2)


Fig. 1. Robots similar to those used in microelectronics for chip production can also be employed for biochip preparation.



Fig. 2. After the reaction of the fluorescent test specimens with the biochip the chip is scanned by a laser, illuminating the points of DNA application one after another and monitoring the fluorescence signal.

Broadly speaking, a mixture of gene products, RNA of different types, is extracted from a cell. The experiment yields information on which gene product can be found in a cell under particular conditions. RNA molecules of each type are associated with a single type (in the ideal case) of molecule immobilized on the chip. The molecules that are not bound can be washed away. The test RNA is labeled with fluorescent dye so it shows its location on the chip, displaying which type of immobilized cDNA has "partners" in the studied cell.
The next stage of the experiment is the biochemical reaction during which one or several DNA or RNA specimens obtained from a cell or tissue are labeled with one or several fluorescent dyes and are hybridized (associated) with the material printed on the chip.
After the reaction of the fluorescent test specimens with the biochip the chip is scanned by a laser, illuminating the points of DNA application one after another and monitoring the fluorescence signal. (Fig. 3)
Biochip preparation takes from three to six weeks, provided that the genetic material for printing is at hand. The experiment itself, hybridization and data scanning takes one or two days. Using traditional technology a group of scientists would have spent years working on successive experiments now included in the single chip.

This on-line version of the book "Biomediale. Contemporary Society and Genomic Culture" is not full. The unabridged edition can be purchased in printed form as anthology. Requests should be sent to: bulatov@ncca.koenig.ru (full information) or in written form: 236000, Russia, Kaliningrad, 18, Marx str., The National Publishing House “Yantarny Skaz”. Phone requests: Kaliningrad +7(0112)216251, Saint-Petersburg +7(812)3885881, Moscow +7(095)2867666. On-line bookshop (in Russian): http://www.yantskaz.ru. Full reference to this book: "Biomediale. Contemporary Society and Genomic Culture". Edited and curated by Dmitry Bulatov. The National Centre for Contemporary art (Kaliningrad branch, Russia), The National Publishing House “Yantarny Skaz”: Kaliningrad, 2004. ISBN 5-7406-0853-7

However biochemical technology has mainly been developed in US public and private research centers. Now, a researcher can order a specialized biochip at many firms, including Affimetrix and Clontech. Others, such as Incyte, can not only produce a specialized biochip and the genetic material for printing but also perform hybridization and supply the final data to a customer. Progress in the industry has been so significant that a market developed for specially treated glass plates for biochip preparation within a common lab with huge producers like Corning.


Fig. 3. A special treatment of the glass surface is necessary before immobilization and the printed biochip should be treated with UV stimulated chemical bonding between the DNA molecules and the glass.

What are the problems that can be solved by such a complicated technology, dealing simultaneously with hundreds of thousands of genes? It should be noted that the most popular chips now contain not thousands but only several hundreds of genes selected to solve a particular biological problem. Let us consider one example. Researchers from MIT used biochips to classify leukosis subtypes, which is of principal value in choosing a therapy. The initial chip contained 6000 test genes. Using test RNA from marrow the researchers successfully identified 50 genes substantially different in their expression patterns. These 50 genes were selected for use in the smaller chip, which could reliably determine the tumor type. (Fig. 4) The high importance of diagnostic chips is obvious, and with a smaller number of analytical elements in this chip, hence lower production costs, it is possible to develop and produce such chips in countries with limited resources including Russia.
The application of biochips is limitless in fundamental life science. A group of researchers from Illinois University led by Prof. A. Gudkov used cDNA chips to identify and compare genes responsible for cell reaction to different types of radiation. A cell recognizes radiation as a stress factor and reacts to it by switching on the gene cascade starting from gene p53, responsible for cell protection from any harmful affects. Many appearing proteins are important for developing new procedures of tumor chemotherapy or for protecting normal cells from anti-tumor agents, such as radiation and chemical drugs.


Fig. 4. Using test RNA from marrow the researchers successfully identified 50 genes substantially different in their expression patterns. These 50 genes were selected for use in the smaller chip, which could reliably determine the tumor type.

A interesting study, from a practical point of view, has been conducted by scientists from the Laboratory of Radiobiology in Helsinki. They used biochips to find out which genes change their activity when affected by a 900MHz radio signal, used in many mobile phone models. Cells from basal layers of human skin were exposed to such a signal for one hour, after which RNA from these cells was tested on a chip together with RNA from the control cells. Genes whose activity changed in such experiments were the stress-response genes such as p53, hsp27 and others, the activity of which usually indicates that a cell or the organism as a whole is experiencing some adverse conditions. Thus, one can cautiously conclude that direct indications of the stress inducing affect of electromagnetic fields have been observed as well as some data on the biochemical background of its biological action. It is not improbable that people who spend less time talking on their cellular phone during the daytime or using headsets are less tired in the evening.

This on-line version of the book "Biomediale. Contemporary Society and Genomic Culture" is not full. The unabridged edition can be purchased in printed form as anthology. Requests should be sent to: bulatov@ncca.koenig.ru (full information) or in written form: 236000, Russia, Kaliningrad, 18, Marx str., The National Publishing House “Yantarny Skaz”. Phone requests: Kaliningrad +7(0112)216251, Saint-Petersburg +7(812)3885881, Moscow +7(095)2867666. On-line bookshop (in Russian): http://www.yantskaz.ru. Full reference to this book: "Biomediale. Contemporary Society and Genomic Culture". Edited and curated by Dmitry Bulatov. The National Centre for Contemporary art (Kaliningrad branch, Russia), The National Publishing House “Yantarny Skaz”: Kaliningrad, 2004. ISBN 5-7406-0853-7

Moreover, the strategy of the biological experiment would also change. Since the computer-aided analysis of data would be the main way of drawing conclusions on the operation of a biological system, the main objective of the biological experiment would be not the direct verification of some idea, as it is now, but streamlining the work of the automated system of information storage and processing. We observe something of this kind already in high energy physics, where computers are used to calculate the effects from known theories, and the experiments are often performed not to specify or check physical foundations and the values of constants, but to improve approximations made during computer simulations of physical processes and to find the best parameters for simulation algorithms.




Fig. 5. Biotech is novel because is based on the idea that the body's own biological processes can be re-designed and re-engineered towards new ends.

One can hope that the software for industrial biomedicine can be created and produced in Russia. The cost of the work in this area is not high, and a significant share of it comprises the labor costs. This is quite the opposite of the situation with traditional molecular biology research, with its expensive reagents and equipment. Powerful supercomputers are not required, in the majority of US scientific centers low-price clusters of PC are used. Which is really required is the high proficiency of researchers in mathematical statistics together with ingenuity and determination, which always was our stronger side.
The only Russian organization seriously involved in the development of biochips technology appears to be the Engelhardt Institute of Molecular Biology, Russian Academy of Sciences. This institute also designs other versions of biochips such as biochips containing test chemical or enzyme reactions.


Fig. 6. Advances in biotechnology have proved to be impossible without specialized hard- and software.

Biochips in EIMB RAS have been developed since 1989, and at several stages it collaborated closely with US labs. EIMB RAS holds 15 international patents as well as many Russian ones. More detailed information can be found at: <http://www.biochip.ru/>





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COLOPHON

CONTENTS:

I. LABORATORY: science and technology

Svetlana Borinskaya. Genomics and Biotechnology: Science at the Beginning of the Third Millennium.

Mikhail Gelfand. Computational Genomics: from the Wet Lab to Computer and Back.

Irina Grigorjan, Vsevolod Makeev. Biochips and Industrial Biology.

Valery Shumakov, Alexander Tonevitsky. Xenotransplantation as a Scientific and Ethic Problem.

Abraham Iojrish. Legal Aspects of Gene Engineering.

Pavel Tishchenko. Genomics: New Science in the New Cultural Situation.
II. FORUM: society and genomic culture

Eugene Thacker. Darwin's Waiting Room.

Critical Art Ensemble. The Promissory Rhetoric of Biotechnology in the Public Sphere.

SubRosa. Sex and Gender in the Biotech Century.

Ricardo Dominguez. Nano-Fest Destiny 3.0: Fragments from the Post-Biotech Era.

Birgit Richard. Clones and Doppelgangers. Multiplications and Reproductions of the Self in Film.

Sven Druehl. Chimaera Phylogeny: From Antiquity to the Present.
III. TOPOLOGY: from biopolitics to bioaesthetics

Boris Groys. Art in the Age of Biopolitics.

Stephen Wilson. Art and Science as Cultural Acts.

Melentie Pandilovski. On the Phenomenology of Consciousness, Technology, and Genetic Culture.

Roy Ascott. Interactive Art: Doorway to the Post-Biological Culture.
IV. INTERACTION CODE: artificial life

Mark Bedau. Artificial Life Illuminates Human Hyper-creativity.

Louis Bec. Artificial Life under Tension.

Alan Dorin. Virtual Animals in Virtual Environments.

Christa Sommerer, Laurent Mignonneau. The Application of Artificial Life to Interactive Computer Installations.
V. MODERN THEATRE: ars genetica

George Gessert. A History of Art Involving DNA.

Kathleen Rogers. The Imagination of Matter.

Brandon Ballengee. The Origins of Artificial Selection.

Marta de Menezes. The Laboratory as an Art Studio.

Adam Zaretsky. Workhorse Zoo Art and Bioethics Quiz.
VI. IMAGE TECHNOLOGY: ars chimaera

Joe Davis. Monsters, Maps, Signals and Codes.

David Kremers. The Delbruck Paradox. Version 3.0.

Eduardo Kac. GFP Bunny.

Dmitry Bulatov. Ars Chimaera.

Valery Podoroga. Rene Descartes and Ars Chimaera.
VII. METABOLA: tissue culture and art

Ionat Zurr. Complicating Notions of Life - Semi-Living Entities.

Oron Catts. Fragments of Designed Life - the Wet Palette of Tissue Engineering.
VIII. P.S.

Dmitry Prigov. Speaking of Unutterable.

Wet art gallery

Biographies

Bibliography

Webliography

Glossary


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