The Emergence of Biotechnology

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The Emergence of Biotechnology

Overview

James Watson (1928- ) and Francis Crick's (1916- ) publication on April 25, 1953, of the double helix model for deoxyribonucleic acid (DNA) propelled the biological sciences and biotechnology, the use of microorganisms to produce specific chemical compounds, into the modern age. Today, biotechnology and molecular biological techniques, once strictly confined to the realm of geneticists and molecular biologists, are finding applications in fields ranging from medicine to species conservation.

Background

Microorganisms, such as yeast, have enhanced the quality of human life for thousands of years. Primitive civilizations used simple forms of biotechnology as they fermented juices to produce alcoholic beverages. By the mid-1700s, microorganisms had been incorporated into cheese, bread, and beverage production. In the 1920s, Alexander Fleming (1881-1955) serendipitously discovered that a mold produced the chemical substance penicillin, which became the first antibiotic used to fight infection. During the next 25 years, as more antibiotics were isolated from microorganisms, early immunology was limited by the amount of the desired chemical substance that these microorganisms could produce naturally.

While immunologists studied microorganisms, their products, and the effects of these products on disease, biologists in other fields were working with other experimental systems to unravel biological mysteries. Experimental, or model, systems were often selected by each scientific discipline for both practical and research purposes. On the practical side, as a body of knowledge grew with regard to one model system, continuing to study that system rather than starting at the beginning again with another species was more efficient. Animal, plant, and bacterial systems were selected on the basis of short life cycles and their similarities to other more complex systems as well as how well these organisms lent themselves to experimental manipulation.

Initially, embryologists utilized frogs, Xenopus laevis and Rana pipen, as model systems for studies of vertebrate development. Fertilized eggs were easily obtained and manipulated. Frog eggs and embryos proved particularly hardy and well-suited for translocation, the movement of cells from one location to another. Later, the mouse, chick, and—most recently—zebrafish were added to the list of model organisms. With a life cycle of nine weeks from fertilization to maturity, the mouse, however, remains the most efficient model system for studying mammalian development.

The fruit fly, Drosophila melanogaster, has been and remains one of the premier tools of the geneticist's trade. Drosophila's attractiveness as a model system stems from its diploid (having two copies of each chromosome) nature—a characteristic it shares with other animals, including mice and humans—and its short life cycle. Even in the absence of modern molecular techniques, Drosophila became invaluable in the study of the effects of mutation because of the fly's many phenotypic markers (readily observable physical characteristics) and the large number of offspring generated quickly from specifically designed genetic crosses. These features permitted early geneticists to map chromosomal mutations and, more specifically, X-linked mutations, from which were extrapolated the implications for human X-linked diseases. Full exploration of mutations as the result of gene expression, however, had to wait until the molecular details of gene expression were uncovered by François Jacob (1920- ) and Jacques Monod (1910-1976) in 1961.

While the contributions of animal and plant models to the fields of embryology, genetics, and molecular biology cannot be overstated, knowledge of these systems (and the systems they represent) have been tremendously affected by that which is not so easily seen—bacteria, viruses, and plasmids. The structural simplicity of these model systems provided the drawing board on which the modern story of molecular biology has been written.

As a result of a series of genetic and biochemical experiments using the common intestinal bacterium, Escherichia coli, Jacob and Monod proposed that clusters of genes with a related function belonged to a single regulatory unit, an operon, in which all of the genes within the cluster are turned on and off together. Thus, these clusters operate as units of transcription and regulation.

While Jacob and Monod were ferreting out the mechanism for gene expression, Francis Crick and Sydney Brenner (1927- ) worked on deducing the nature of the genetic code. Charles Yanofsky's (1925- ) studies of tryptophan sythetase in E. coli confirmed that a sequence relationship existed between DNA and the proteins it encodes. Crick and Brenner set out to figure out how many nucleotides were necessary to specify each amino acid. Through careful studies of the effects of the mutagen proflavin on a bacteriophage, a virus that only infects bacteria, Crick and Brenner concluded that nucleotides in DNA must be read in groups of three. Within five years of Crick and Brenner's publication of the triplet nature of the genetic code, the genetic code was cracked. Many advances in molecular biology during the 1960s came from studies of E. coli and of bacteriophages and plasmids that use it as a host.

The 1970s were host to an avalanche of technical discoveries that led to dramatic advances in molecular cell biology. The discovery of restriction enzymes, enzymes found in most bacterial cells that protect the cell from foreign DNA, in 1971 was a boon to molecular biologists. Restriction enzymes enabled biologist to cut DNA from any organism at specific sequences thereby generating a reproducible set of fragments. The isolation or determination of fragment lengths was accomplished using gel electrophoresis. Analysis of variability in the lengths of fragments was then added to the molecular biologist's tool box. Restriction fragment length polymorphism (RFLP) analysis proved to be particularly useful in the study of genetic variability within and between species.

By 1973, Stanley Cohen (1922- ) and Herbert Boyer had used DNA fragments and ligases, enzymes normally involved in DNA replication and repair, to produce the first recombinant DNA organism. The insertion of a restriction fragment containing specific genetic information into a bacterial genome gave birth to the new science of recombinant DNA technology, which now includes cloning and genetic engineering.

While there have been major biotechnological advances made since 1973, none have so profoundly affected molecular biology as the development of the polymerase chain reaction (PCR), developed in 1985. Using PCR techniques, very small samples of genomic DNA can be amplified, resulting in sample sizes large enough to carry out standard DNA analysis protocols. This technology has made significant contributions to many fields, including law enforcement, immunology, and conservation biology.

Impact

Medicine is at the forefront of the biotechnology revolution. After his groundbreaking work with Cohen, Boyer co-founded Genentech, the first biological engineering company. Genentech pioneered the bioengineering industry, producing the first bioengineered human protein, insulin, and human growth hormone, which is used in the treatment of children. By 1982, Genentech had begun marketing genetically engineered insulin, thereby changing the pharmaceutical industry. Today, through the aid of bioengineering, the volume of natural antibiotics produced by microorganisms no longer limits the work of immunologists as they now have synthetic and recombinant weaponry in their arsenal against disease. Additionally, innovative treatments for age-old diseases such as cystic fibrosis and muscular dystrophy are giving some patients afflicted with these diseases a new lease on life through gene therapy.

As science gains a fuller understanding of genes—how they operate and how they can be manipulated—science endeavors to attack disease at its foundation. Since many diseases are rooted in missing or flawed genes, physicians and molecular biologists are striving together to correct genomic problems through gene therapy. Healthy copies of genes that compensate for faulty genes are the focus of the gene therapy industry.

Second only to the focus on biotechnological applications in medicine is the impact of advances in molecular techniques on agriculture. As agriculturists endeavor to improve crop yield and quality while at the same time reducing production costs, bioengineers are increasingly called upon to accomplish these tasks. Bioengineered plants are expected to reduce the amount of fertilizer and pesticide needed to ensure high crop yields.

In addition to the health care and agricultural industries, advances in molecular techniques have significantly influenced other social and natural sciences. For example, the discovery of restriction enzymes and the fragments that they generate has been used to examine phylogenetic relationships within and between species. Southern, Western, and Northern Blot techniques as well as RFLP analysis, DNA amplification using PCR technology, and DNA sequencing represent only a short list of the molecular techniques employed to investigate species relatedness (the time since the evolutionary divergence between two species) and levels of genetic variability (a measure used to evaluate species health and viability) in captive and wild populations.

The twentieth century witnessed rapid and remarkable advances in science and medicine. Life expectancy in developed nations at the time of Watson and Crick's 1953 publication was approximately 66 years. As a result of monumental advances in both biological knowledge and biotechnology—less than 50 years after Watson and Crick's historic discovery—many individuals living in industrialized nations can expect to live well into their 70s or beyond. Similarly, through better health care and reproductive technology, infant mortality in developed nations is at its lowest level in history. The results of the Human Genome Project, slated for release in 2003, will mark the fiftieth anniversary of the publication of the double helix model of DNA. With information on every gene sequence in the human genome expected to be available, the twenty-first century is already being referred to as the "biology century."

MICHELLE ROSE