Bunch-Hellemans, Genetic engineering

Genetic engineering consists of a set of methods to change the genes of an organism so that proteins produced by that organism differ in type or quantity from those produced by a “wild” organism –– one that has not been altered. Although people have been causing such changes in organisms since domestication began about 10,000 years ago, the phrase genetic engineering conventionally refers to a set of techniques that became possible only in 1973.

It is easy to think that genetic engineering was the inevitable outcome of the Watson-Crick explanation of the mechanism of heredity in 1953, but that is not really the case. While knowledge of DNA structure and the genetic code is essential to genetic engineering, the path that led to practical results was separate from the path that led to understanding. Along the way, of course, both paths interacted constantly. The path that led to practical applications could not have been predicted in advance, as almost all of the important discoveries were previously unsuspected by any scientist.

The start of the path toward genetic engineering occurred in 1952 when Joshua Lederberg discovered that bacteria, like some protists, conjugate to exchange genetic material. This behavior, much like sex in multicellular organisms, led Lederberg to perceive that there are two populations of bacteria, which he called M and F. The F population contains a body that he called a plasmid.

After conjugation, the F bacterium passes the plasmid on to the M bacterium, with which it has conjugated. (It would appear that Lederberg had his sexes backward, but that is not essential to what follows.) This discovery was completely surprising. The next year William Hayes established that the plasmid consists of genetic material. By then it was clear that genes are DNA; therefore, plasmids are rings of DNA floating free of the main DNA of a bacterium.

About the same time, an apparently unrelated situation became a major problem. Both the sulfa drugs and the antibiotics of the late 1930s and 1940s were, in the 1950s, beginning not to work as well as they had. Many bacteria were becoming resistant to those drugs. Epidemics, especially in hospitals, could no longer be controlled. Many scientists studied the problem. In 1959 Japanese scientists discovered that the genes for drug resistance were carried on plasmids, and therefore passed from bacterium to bacterium. Within a given bacterium, the plasmids multiplied, so there were plenty of copies to pass around. Inserting a few drug-resistant bacteria into a colony of bacteria that showed no resistance resulted in short order in a colony that was completely resistant.

It is not surprising that some bacteria had plasmids that protected against these drugs. Antibiotics are natural substances found in the environment, so some bacteria have evolved defenses against them. The increase in the amount of antibiotics caused by human intervention led to the resistant bacteria passing the plasmids around to larger populations.

In the meantime, another line of research was also leading toward genetic engineering. Starting right after World War II, a number of biologists made an intensive study of viruses that infect bacteria, which are collectively called bacteriophages, or just phages. This line of research demonstrated that genes are part of DNA and not part of a protein, as had previously been suspected. As early as 1946 Max Delbrück and Alfred Hershey independently showed that the genes from different phages could spontaneously combine. Werner Arber studied the mutation process in phages in detail. In the process he discovered that bacteria resist phages by splitting the phage DNA with enzymes.

Subsequent recombination of split genes was a consequence of this. By 1968 Arber had located the enzymes that split DNA at specific locations. The split ends are “sticky”; that is, different genes that have been split at the same location by one of these restriction enzymes, as they came to be called, will recombine when placed together in the absence of the enzyme. The resulting product is called recombinant DNA.

The following year, 1969, Jonathan Beckwith and coworkers became the first to isolate a single gene. It was a bacterial gene for a part of the metabolism of sugar. In 1973 Stanley Cohen and Herbert Boyer combined the restriction enzymes with plasmids with isolation of specific genes to introduce genetic engineering. They cut a chunk out of a plasmid found in the bacterium Escherichia coil and inserted into the opening a gene from a different bacterium. Then they put the plasmid back into the bacteria E. coli, where copies were made and transferred to other bacteria. Within months other scientists repeated the trick, inserting genes from fruit flies and frogs into E. coli.

Not all scientists thought this was a good thing. In July 1974, Paul Berg and other biologists met under the auspices of the U.S. National Academy of Sciences to draw up guidelines that would prohibit certain kinds of genetic engineering. Since 1974, the tension between those who are rapidly advancing genetic engineering and those who worry about where it is going has continued. By the 1980s, the genetic engineers were producing useful products from bacteria and yeasts, including human growth hormone, human insulin, and a vaccine for hepatitis B. All these are made in tanks in controlled environments and have ceased to evoke much resistance from scientists or the public. There has been more resistance to experiments in which genetically engineered bacteria are released in the environment, although a number of small-scale releases have so far not resulted in known environmental damage. Another source of concern relates to the safety of the many farm crops that have been modified by genetic engineering.

In one area, the progress of genetic engineering has been frustratingly slow. From the beginning of the new technique, there has been hope that it could be used to cure human genetic diseases. So far, that has not proved practical in most cases, although there has been some limited success.

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