Genetically Engineered Organism

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Genetically engineered organism

The modern science of genetics began in the mid-nineteenth century with the work of Gregor Mendel, but the nature of the gene itself was not understood until James Watson and Francis Crick announced their findings in 1953. According to the Watson and Crick model, genetic information is stored in molecules of DNA (deoxyribose nucleic acid ) by means of certain patterns of nitrogen base that occur in such molecules. Each set of three such nitrogen bases were codes, they said, for some particular amino acid , and a long series of nitrogen bases were codes for a long series of amino acids or a protein.

Deciphering the genetic code and discovering how it is used in cells has taken many years of work since that of Watson and Crick. The basic features of that process, however, are now well understood. The first step involves the construction of a RNA (ribonucleic acid ) molecule in the nucleus of a cell, using the code stored in DNA as a template. The RNA molecule then migrates out of the nucleus to a ribosome in the cell cytoplasm. At the ribosome, the sequence of nitrogen bases stored in RNA act as a map that determines the sequence of amino acids to be used in constructing a new protein.

This knowledge is of critical importance to biologists because of the primary role played by proteins in an organism. In addition to acting as the major building materials of which cells are made, proteins have a number of other crucial functions. All hormones and enzymes, for example, are proteins, and therefore nearly all of the chemical reactions that occur within an organisms are mediated by one protein or another.

Our current understanding of the structure and function of DNA makes it at least theoretically possible to alter the biological characteristics of an organism. By changing the kind of nitrogen bases in a DNA molecule, their sequence, or both, a scientist can change the genetic instructions stored in a cell and thus change the kind of protein produced by the cell.

One of the most obvious applications of this knowledge is in the treatment of genetic disorders. A large majority of genetic disorders occur because an organism is unable to correctly manufacture a particular protein molecule. An example is Lesch-Nyhan syndrome. It is a condition characterized by self-mutilation, mental retardation, and cerebral palsy which arises because a person's body is unable to manufacture an enzyme known as hypoxanthine guanine phosphoribosyl transferase (HPRT).

The general principles of the techniques required to make such changes are now well understood. The technique is referred to as genetic engineering or genetic surgery because it involves changes in an organism's gene structure. When used to treat a particular disorder in humans, the procedure is also called human gene therapy. Developing specific experimental techniques for carrying out genetic engineering has proved to be an imposing challenge, yet impressive strides have been made. A common procedure is known as recombinant DNA (rDNA) technology.

The first step in an rDNA procedure is to collect a piece of DNA that carries a desired set of instructions. For a genetic surgery procedure for a person with Lesch-Nyhan syndrome, a researcher would need a piece of DNA that codes for the production of HPRT. That DNA could be removed from the healthy DNA of a person who does not have Lesch-Nyhan syndrome, or the researcher might be able to manufacture it by chemical means in the laboratory.

One of the fundamental tools used in rDNA technology is a closed circular piece of DNA found in bacteria called a plasmid. Plasmids are the vehicle or vector that scientists use for transferring new pieces of DNA into cells. The next step in an rDNA procedure, then, would be to insert the correct DNA into the plasmid vector. Cutting open the plasmid can be accomplished using certain types of enzymes that recognize specific base sequences in a DNA molecule. When these enzymes, called restriction enzymes, encounter the recognized sequence in a DNA molecule, they cleave the molecule. After the plasmid DNA has been cleaved and the correct DNA mixed with it, a second type of enzyme is added. This kind of enzyme inserts the correct DNA into the plasmid and closes it up. The process is known as gene splicing.

In the final step, the altered plasmid vector is introduced into the cell where it is expected to function. In the case of a Lesch-Nyhan patient, the plasmid would be introduced into the cells where it would start producing HPRT from instructions in the correct DNA. Many technical problems remain with rDNA technology, and this last step has caused some of the greatest obstacles. It has proven very difficult to make introduced DNA function. Even when the plasmid vector with its new DNA gets into a cell, it may never actually begin to function.

Any organism whose cells contain DNA altered by this or some other technique is called a genetically engineered organism. The first human patient with a genetic disorder who is treated by human gene therapy will be a genetically engineered organism. The use of genetic engineering on human subjects has gone forward very slowly for a number of reasons. One reason is that humans are very complex organisms. Another reason is that changing the genetic make-up of a human involves more ethical questions and more difficult questions than does the genetic engineering of bacteria, mice, or cows.

Most of the existing examples of genetically engineered organisms, therefore, involve plants, non-human animals, or microorganisms . One of the earliest success stories in genetic engineering involved the altering of DNA in microorganisms to make them capable of producing chemicals they do not normally produce. Recombinant DNA technology can be used, for instance, to insert the DNA segment or gene that codes for insulin production into bacteria. When these bacteria are allowed to grow and reproduce in large fermentation tanks, they produce insulin. The list of chemicals produced by this mechanism now includes somatostatin, alpha interferon, tissue plasminogen activator (tPA), Factor VIII, erythroprotein, and human growth hormone, and this list continues to grow each year.

[David E. Newton ]