By Robert Hazen, George Mason University
Genetic engineering is the process of consciously altering a coded sequence of DNA or RNA. We have a remarkable toolbox of various kinds of enzymes that can cut, paste, rearrange, and copy DNA; all sorts of things to manipulate DNA can be done in the laboratory. These methods, together with sophisticated chemical techniques and analytical tools, comprise this entire toolkit for the molecular biologist, for the genetic engineer.
Genetic Toolkit
Virtually, any desired sequence of nucleotides can now be synthesized. We can take that sequence of DNA and introduce it into a cell. Furthermore, with some experimental organisms, it’s even possible to remove specific pieces of DNA.
The genetic toolkit includes techniques that can be used to quickly and accurately compare the DNA from different organisms—for screening hereditary diseases, mapping evolutionary pathways, controlling which viruses come from which places, monitoring bacterial infections, an d even identifying criminal suspects. These are all part of the genetic toolkit. But genetic engineering, actually modifying the genome, is another step in this process.
This is a transcript from the video series The Joy of Science. Watch it now, on Wondrium.
Genomes in Bacteria
The earliest efforts in genetic engineering focused on the large-scale production of various proteins that were essential in medicine; and other areas also, for example, in food production, for various kinds of basic research. These all employ single-celled bacteria that reproduce very quickly, so one had many generations of bacteria to work with.
Bacteria have very simple genomes. The simplest bacteria, like E. coli, have loops of DNA that are called plasmids. A plasmid is nothing more than a genome that is a closed loop. We wouldn’t call it a chromosome because it’s too small an amount of genetic material, and yet it contains genetic information.
In the simplest genetic engineering protocols, bacterial cells are exposed to strands of DNA with a desirable gene on them. The DNA can be from any other organism: a human being, a plant, or anything else. We expose the bacteria to these genes. The DNA may even be in the form of a virus because we can sometimes get a virus to incorporate a new protein. It’s difficult to target the correct part of a bacterial genome, so when we insert new DNA material, it may be incorporated into the genome or it may not be; it may be incorporated into a place where it can’t be expressed, and it goes unnoticed.
Multiplying Bacterium
However, once in a while, if we expose the bacterium to a specific gene, that gene may be incorporated in such a way that it can be expressed, and the bacteria can actually make some of the protein for which that gene codes. Given enough bacteria, a few cells may actually be successful. Then it just becomes a brute-force method where we expose lots and lots of cells to the desired gene, and then extract the few cells that have successfully incorporated that particular gene.
Once we have a single bacterium that has the correct gene and expresses it, then that bacterium can be moved and isolated, and it starts multiplying on its own and makes more and more copies of itself. Where we had one bacterium before, we’re going to have countless numbers, if we give it the appropriate environment in which to grow and develop.
Uses by Pharmaceutical Companies
Dramatic early successes of this kind included the development of E. coli strains that were engineered to contain specific genes for components of human insulin, for example, and also synthetic growth hormone. Prior to this technology, anyone who was a diabetic had to take insulin from another animal, for example, pig insulin, which is not identical to human insulin. But in this particular case, we can actually engineer insulin which is identical to human insulin, so it’s much more effective for diabetics.
Pharmaceutical companies culture these bacteria in huge vats to produce the desired proteins in commercial quantities. We have lots of bacteria, and they are literally our chemical factories that are producing this specific enzyme that we want. All we need to begin, now, is one successful bacterium, one successful microbe that duplicates itself over and over again.
Genetic Diseases
Bacteria can manufacture huge quantities of whatever protein we want, as long as we can get them to start doing this technique. Then the proteins can be purified; we can make crystals of them by purifying, extracting, and crystallizing them out; then we can do X-ray structure studies, for example, on hemoglobin, or on other proteins. This is an important way of discovering protein structures, by starting with microbes.
This whole technique has proven especially valuable in studies of defective proteins, that is, proteins that are designed intentionally to incorporate one or more amino acid mistakes. If we understand the behavior of a mutant protein, then we can gain insight on the function of enzymes when they’re working correctly. We also can get a feeling for what causes genetic diseases, because genetic diseases are nothing more than genes that are producing proteins that are defective, proteins with the wrong shape.
For example, damaging one protein in mice causes the animals to become gluttonous. They overeat, and they begin to get fat. Eventually, they gain so much weight that they can hardly move around their cages. We now know that that particular target protein acts as a hunger suppressant of some kind, and very similar genes occur in humans; this may be a key to overeating diseases of certain sorts.
This research would not be possible except for genetic engineering.
Common Questions about What Makes Genetic Engineering Valuable
The genetic toolkit includes techniques that can be used to compare, quickly and accurately, the DNA from different organisms—for screening hereditary diseases, for mapping evolutionary pathways, for controlling which viruses come from which places, for monitoring bacterial infections, and for even identifying criminal suspects.
A plasmid is a genome that is a closed loop. The simplest bacteria, like E. coli, have loops of DNA that are called plasmids.
E. coli strains have been developed and engineered to contain specific genes for components of human insulin. Prior to this, anyone who was a diabetic had to take insulin from another animal, for example, pig insulin, which is not identical to human insulin. But now, we can actually engineer insulin which is identical to human insulin, so it’s much more effective.
