Biotechnology and Genetic Engineering, History of

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Biotechnology and Genetic Engineering, History of

The term "biotechnology" dates from 1919, when the Hungarian engineer Karl Ereky first used it to mean "any product produced from raw materials with the aid of living organisms." Using the term in its broadest sense, biotechnology can be traced to prehistoric times, when huntergatherers began to settle down, plant crops, and breed animals for food. Ancient civilizations even found that they could use microorganisms to make useful products, although, of course, they had no idea that it was microbes that were the active agents. About B.C.E. 7000, the Sumarians and Babylonians discovered how to use yeast to make beer, and winemaking dates from biblical times. In about B.C.E. 4000, the Egyptians found that the addition of yeast produced a light, fluffy bread instead of a thin, hard wafer. At the same time, the Chinese were adding bacteria to milk to produce yogurt.

Genetic Engineering versus Biotechnology

For many, the term "biotechnology" is often equated with the manipulation of genes, but, as Ereky's definition suggests, this is only one aspect of biotechnology. For the more specific technique of gene manipulation, the term "genetic engineering" is more appropriate. Genetic engineering dates from the 1970s. At that time molecular biologists devised methods to isolate, identify, and clone genes as well as to mutate, manipulate, and insert them into other species. One of the key elements in such research was the discovery of restriction enzymes . These enzymes are able to cleave DNA at a limited number of sequence-specific sites and often leave "sticky ends." Isolated DNA from any organism could be cleaved with a restriction enzyme and then mixed with a preparation of a vector that had been cleaved with the same restriction endonuclease. By virtue of the "sticky ends," a hybrid molecule could be created that contained the gene of interest, which could then be inserted into such a cloning vector. The importance of restriction endonucleases was recognized in 1978 by the awarding of the Nobel Prize in physiology or medicine to Werner Arber, Daniel Nathans, and Hamilton Smith for their discovery of these enzymes.

Further Advances and Ethical Concerns

The first experiment to combine different DNA molecules was performed in 1972 in the laboratory of Paul Berg (who shared the 1980 Nobel Prize in chemistry for this work). The following year Stanley Cohen and Herbert Boyer combined some viral DNA and bacterial DNA in a plasmid to create the first recombinant DNA organism.

Realizing the potential dangers of moving genes from one organism to another, approximately ninety prominent scientists, whose laboratories were poised to start cloning experiments, met in 1975 at the Asilomar Conference Center in California to discuss the potential dangers of gene manipulation. This meeting, wherein scientists recognized and openly discussed the ramifications and potential dangers of their research before that research was actually begun, was unprecedented. The result of the Asilomar Conference was to call for and agree upon a one-year moratorium before any cloning experiments were to be done. This provided time to develop guidelines for the physical and biological isolation of recombinant organisms, to ensure that they not escape into the environment, and, if they did, to make sure that they would be so weakened as not to survive competition with naturally occurring organisms. By 1976, then, gene cloning was in full swing around the world.

Key Technical Developments

Advances in biotechnology were marked by the development of key research techniques. In 1976, Herbert Boyer and Robert Swanson founded Genentech, the first biotechnology company to use recombinant DNA technology in developing commercially useful products such as drugs. The year 1977 is considered the "dawn of modern biotechnology," for it was in that year that the first human protein was cloned and manufactured using genetic engineering technology: Genentech reported the cloning of the human hormone somatostatin. This year was also important for the development of the technique of DNA sequencing, achieved by Fred Sanger and Walter Gilbert (who, with Paul Berg, shared the 1980 Nobel Prize in chemistry).

In 1978 Genentech was able to isolate the gene for human insulin and begin clinical trials that resulted in the approval and marketing of the first genetically engineered drug for human use. This was a major accomplishment. Diabetes, the seventh leading cause of death in the United States, affects millions of Americans. In the past, insulin was extracted from the pancreases of cows or pigs, then used to treat diabetics. Although insulin from these species is very similar to human insulin and was effective in humans, the small differences between human and animal insulin were enough to cause problems for some patients. Often patients developed immunological reactions to the foreign protein, reducing its effectiveness. With the availability of genetically engineered human insulin, these problems were eliminated.

Patents and the Rise of Biotechnology Companies

In 1980 the U.S. Supreme Court provided an important incentive for the development of biotechnology companies. In the case of Diamond v. Chakrabarty, the court ruled that biological materials may be patented. Thus, private companies could look forward to making substantial profits from therapies that they developed through genetic engineering techniques.

Among the new companies to take advantage of the court ruling was the Chiron corporation, which cloned the protein that formed the outer coat of the human hepatitis B virus. This protein, which could now be produced without the virus that it normally enclosed, provided the material for the development of the first human vaccine using recombinant DNA technology. The hepatitis vaccine has been available since 1987.

In the same year, the Food and Drug Administration (FDA) approved Genentech's drug tPA (tissue plasminogen activator). This is a human blood protein that helps to dissolve fibrin, the major protein involved in forming blood clots at the site of an injury. After the healing process is complete and clotting is no longer required at the site of the injury, the body normally releases tPA to activate an enzyme called plasmin, which dissolves fibrin. However, it was discovered that tPA could also be used as a powerful drug in the treatment of certain heart attacks. Sometimes a blood clot forms spontaneously in the body. If the clot forms or lodges in the coronary arteries of the heart, the clot blocks blood flow to the heart muscle, resulting in what is commonly called a heart attack. If tPA is given to such patients within four hours of onset, the recovery is truly remarkable. Such patients are able to leave the hospital the next day with little or no aftereffects of the heart attack. A patient not treated with tPA often remains in the hospital for a week or longer and can not resume normal activities until after a long recovery period. The drug has subsequently been approved for use with patients suffering a stroke from a blood clot in the brain with similar success.

Biotechnology has also been sucessful in development of other useful products. Today many laundry detergents contain proteases, enzymes that remove stains by digesting the protein components of the stain. However, such enzymes are inactivated by bleach. In 1988 the biotechnology company Genecor received approval for a bleach-resistant protease. This had been accomplished by isolating the gene for protease and then, using sitedirected mutagenesis, changing the gene such that the corresponding protein was no longer sensitive to inactivation by bleach.

Biotechnology has also made a great impact in agriculture. The first genetically engineered plant was patented in 1983. The first genetically engineered food was produced by a company called Calgene, in 1987. Calgene, now a part of Monsanto, produced a tomato that could be ripened on the vine and transported ripe to market. Tomatoes are normally shipped green to market and left to ripen at their destination because they are easily bruised and damaged if shipped when fully ripe. Today there is a new "green revolution" under way, in which genetically modified food will provide greater nourishment and higher yields, while simultaneously reducing the use of fertilizers and herbicides. Although there is considerable controversy surrounding these foods (sometimes referred to as "Frankenfood"), there have been no documented cases of anyone being hurt by eating them. In 1990 the biotech firm GenPharm created a transgenic dairy cow into which the genes for human milk proteins were inserted. The milk from such cows will be used for producing infant formula.

Biotechnology and the Law

Biotechnology has also made important contributions to the field of law. Most notably, scientists have developed exquisitely sensitive methods for identifying DNA. Indeed, with the invention of the polymerase chain reaction in 1988, enough DNA can be extracted from a drop of blood, a tiny shred of skin, a single hair, or a small semen sample to identify the individual from whom it originated. Such "genetic fingerprinting" was developed in 1984 and first used in a trial in 1985.

Perhaps the most famous case involving DNA-based evidence was the O.J. Simpson murder trial in 1995. During the 1990s however, genetic evidence in the courtroom became commonplace and accepted by trial lawyers, judges, and juries alike. In fact, several innocent people were released from prison as a result of the reexamination of evidence using DNA fingerprinting.

The Human Genome Project

In 1990 molecular biologists around the world began working on what ranks as perhaps the greatest achievement of biotechnology, the Human Genome Project, in which the more than 3 billion nucleotides of DNA in the human nucleus were ultimately sequenced. Although DNA sequencing began in 1977, it was the development in the 1990s of automated DNA sequencers and powerful computers to store and analyze the data that made this project feasible. The first draft of the human genome was completed in 2001. With the complete sequence available, scientists will be able to "mine the genome" to find important gene products and to design specific drugs to target gene product. The twenty-first century will see tremendous new advances using biotechnology.

see also Agricultural Biotechnology; Bioinformatics; Biotechnology; Biotechnology Entrepreneur; Cloning Genes; Cloning Organisms; Genetically Modified Foods; Genomics Industry; Human Genome Project; Mutagenesis; Patenting Genes; Plant Genetic Engineer; Restriction Enzymes; Sanger, Fred.

Ralph R. Meyer