Genetic engineering has its origins in plant and animal breeding. Sometime in antiquity, someone observed that like produces like – on the average, if one breeds two strong, healthy brown cows, one gets more strong, healthy brown cows. Change one of the parents to a white cow and you can expect white cows, and maybe even varicolored cows, among the offspring. Do these breedings consistently, periodically going back to a common ancestor to reinforce certain traits, and soon you will have a line that breeds true; that is, that produces individuals of consistent appearance, or phenotype.
The 19th century Augustinian monk, Gregor Mendel, codified these principles through his experiments with pea plants, founding the new science of genetics. His discoveries made it possible for humans to deliberately mold plants and animals in their own vision by selective breeding, revolutionizing agriculture in the process.
The other vital, 19th century contribution to modern genetic engineering methods was made by Charles Darwin, who discovered the principle of natural selection. In its simplest form, this principle states that the species most suited to its environment will predominate over other species that are less suited, and that the genes that confer this suitability will proliferate.
In the middle of the 20th century, James D. Watson, Francis Crick, Maurice Wilkins and Rosalind Franklin discovered the structure of deoxyribonucleic acid (DNA), the genetic material, and proposed a mechanism for its replication. Their mechanism was based on the fact that DNA is composed of four building blocks, called nucleotides, identified as adenine (A), thymine (T), guanine (G) and cytosine (C). These nucleotides form long chains, or stands, which associate with each other in a double helix. In that helix, A is always found across from T, and G is always found across from C, providing a code that allows either strand to be exactly duplicated from the nucleotide sequence of its partner. Along with nuclear fission, this was arguably the most important scientific discovery of the century, for which Watson, Crick and Wilkins won the Nobel prize. This discovery enabled legions of biologists to elaborate on the mechanisms of genetic change elucidated by Mendel in biochemical terms.
Darwin’s theory proposed that genetic change in a population occurs via a process of mutation and selection; that is, a random change in the structure of an organism’s DNA occurs and confers a trait that makes that organism more suited to its environment. Scientists verified this theory by identifying bacterial mutants that were resistant to various antimicrobial substances, and selecting them away from sensitive strains by exposing them to the toxic substance. They also identified particular chemicals, called mutagens, which increased the frequency of the appearance of these resistant strains.
Scientists learned that they could introduce foreign DNA into plant and animals cells by a process called transfection, and that the introduced DNA would integrate into the organism’s DNA, conferring a heritable genetic trait. This process came to be known as genetic engineering.
The next important discovery that allowed modern genetic engineering techniques to be developed was that of enzymes called restriction endonucleases, which cleaved DNA strands at specific nucleotide sequences. This led to the so-called technology of shotgun cloning, where restriction fragments from a donor could be introduced into the cells of a recipient, where they would combine with its DNA The introduced DNA sequence would be perpetuated by subsequent cell division. As always, particular clones with desired genetic traits could be isolated by selection. This technique even allowed the DNAs of different species to be combined in a single organism.
This technology was viewed with apprehension by many, essentially because the introduced genetic material was random. While a specific trait in the recipient could be selected for, it was difficult or impossible to know what other traits may have been introduced along with it. If a genetically altered organism was released inadvertently or deliberately into the environment, where its proliferation could no longer be controlled, many feared that potentially catastrophic consequences. Apprehension was so strong that top scientists in the field called for a voluntary moratorium on certain types of experiments until the practical and ethical implications of the work could be fully considered. Even today, some types of research are controversial – see my post on Scientific Ethics and the Flu for one example.
Modern advances in genetic engineering technology are decreasing this apprehension because they provide much more control over the process. One example is Precision Biosciences’ Directed Nuclease Editor (DNE) technology. Standard restriction endonucleases recognize very short (~5-6) nucleotide sequences. This results in many short DNA fragments when a large piece of DNA is cleaved. The heart of DNE technology is so-called “meganucleases”, which recognize much longer sequences. This allows for excision and purification of specific genes from the donor DNA, provided that the DNA sequences flanking a particular gene are known, eliminating the introduction of nonspecific DNA fragments into the recipient. This technology has many applications – I recently wrote an article for a local newspaper on just one of them.
The future of this technology is exciting! It essentially allows humans to customize organisms for a specific purpose, or to a specific environment. It has tremendous implications for revolutionizing manufacturing and healthcare, eliminating hunger throughout the world, and bringing new industries into impoverished areas. The possibilities are limited only by our imaginations.