How should humanity respond to new technologies allowing for genetic editing and engineering?
A student alive in the 1980s would have been told that computers would soon take over everything. From shopping to gaming, as well as the stock market. It seemed impossible- until it all happened. The world is at a similar point today with genetic engineering where science fiction, once again, is quickly becoming our reality as both human and non-human genetic and reproductive technologies are being swiftly integrated into our lives. The potential applications of these modern technologies raise various legal, ethical and social debates. The use of genetic medicine, foetal screenings, pharmacogenomics, equal access to this new medicine, and discrimination on the basis of genetics are all examples of issues rapidly becoming more relevant and pressing, not only to the scientific community, but also to the global one. Social and ethical standards are central to how the world will govern the way new genetic technologies are transformed into healthcare benefits to individuals and populations. It is important for the global community to participate in the genetic engineering conversation to ensure that further research and application is guided with transparency and jurisdiction. Scientists cannot yet make sound predictions on the risks that genetic engineering pose to unborn children therefore most of the current debate is torn between those with the belief that this research should continue under a regulatory scheme, and those who believe that it is best to ban genetic modification entirely. The crucial difference between the two arguments is that those who favour regulation do not agree that there is anything inherently wrong with the science, while those in opposition see that there are inevitable undesirable ramifications to modifying the human gene pool. The extent of morality of genetic engineering is completely dependent on a sufficient understanding and comprehension of the political, medical, social and ecological consequences of its application.
The instructions for the make-up of all creatures are written in the code of DNA. Despite the massive diversity of life on earth, this system is incredibly conservative. The code for making silk in a spider is written in the same language as the code for making goat’s milk. Since the beginning of genetic engineering, humans have taken advantage of this universal language of genomics to cut and paste DNA from one species into another. This editing technology has progressed to the extent that any sections of DNA code are effectively interchangeable between different species. Genetic modification is not a thing of recent times, humans have been engineering life ever since they made the change from hunter gatherers to farmers. This was done through selective breeding. Parents with the best of the desired characteristics are selected from a mixed population and are bred together. From the offspring produced, those with the desired characteristics are then also bred together. Characteristics can be bred for usefulness or appearance, such as insect resistance in crops, animals producing more meat or dogs gentle in nature and friendly in appearance. The average size of a chicken has increased by four times due to selective breeding for over 50 years. Conventional breeding based on artificial selection can achieve astonishing things; the incredible variety of dogs we have today is due to conventional breeding. Humans quickly became very good at these techniques but never fully understood how exactly they work. This was until the discovery of deoxyribose nucleic acid in 1953, a complex molecule that guides the synthesis, growth, function and reproduction of all living matter. The instructions for this can be found in the structure of the molecule where the four essential nucleotides adenine, guanine, cytosine and thymine are paired and make up a code that carries instructions that dictate our being. A codon of three of those bases correspond to one of twenty amino acids, and in this way our bodies’ most essential proteins are assembled.
It is a widespread belief that our genome is a static, abstract code, a pattern of letters that you’re born with and will die with identically. This approach is rooted in the legacy of genetic determinism, the belief that human behavior is controlled by an individual’s genes, an idea from which stems the movements in science associated with eugenics, scientific racism, the predestination of IQ, and the biological basis for gender roles. These strong deterministic assumptions have been repeatedly proven false in the 20th century by scientists who studied how nature and nurture work together, intertwined to decide the organism’s behavior. Many arguments against genetic modification stem from a strong version of biological determinism which results in an overblown fear of all genetic modification. It is therefore useful to think of our genome as “dynamic” molecules, as put forward by Jorge Fardels to illustrate the flexibility of DNA and its potential to be modified and manipulated through epigenetics. Our chromosomes are physical molecules that can wrap around themselves in a certain way to fit into each of our cells. This wrapping affects which genes are turned on and made into proteins and which remain silent. DNA is littered with methyl groups which can also activate or deactivate genes. Although methylation itself is genetically encoded in ‘methylation landscapes’ of different tissues, it is also influenced by environmental exposures such as diet and stress. Furthermore, the underlying genome itself is not fixed. DNA mutations often take place during cell division, making the daughter cell genetically different. Recently discovered ‘jumping genes’ are further proof of the unfixedness of our genome, sometimes jumping genes use a cut-and-paste technique, other times a copy-and-paste. Once an understanding of the changing nature of our genome is established, the idea of genetic engineering appears less unnatural and may eventually be accepted as simply the next step in our natural evolution as a species.
If 20th-century biology was driven by disassembling organisms and their genomes to discover the details of how they work, this current era is defined by reconstructing them, but not necessarily as dictated by the direction of evolution, and certainly without the unreliable restrictions of mating. Breeding programs, unlike transgenic technology, are constrained by what one can breed together. Transgenic biology however, crosses species barriers giving way to extreme crossbreeding. Organisms that have had genes from other species inserted into their genome are known as ‘transgenic’. Most transgenic organisms are generated in the laboratory for research purposes. Currently, the widest use of transgenic animals is in medical research. A scientist will implant a gene into an animal, then observe how the gene affects the animal’s behaviour and appearance. Alternatively, a specific gene may be inactivated by a genetic technique, and the consequences on the phenotype are observed and recorded. In this way, the functions of numerous genes have been discovered. When a scientist discovers a gene with a strong link to a disease, it is quite likely that they found it using a transgenic animal. This was the case with “oncomice” which are mice that develop tumours excessively and have been used by researchers to develop anticancer drugs. With the use of these transgenic animals, scientists are getting great insight into how cancer works and how to treat it on a molecular level. Transgenics are being applied by thousands of people to better understand many aspects of our biology at the fundamental level.
The first genetically engineered products were pharmaceuticals used to treat human diseases and disorders. These are usually produced by transgenic bacteria. It is interesting that these were once highly controversial because the public feared the use of modified bacteria, but now they are widely accepted and deemed mainstream. This is likely to happen with genetic engineering in humans, as the potential benefits trump the risks. In 1979, Elly Lilly corporation was the first to use E. coli as living factory to produce human insulin. This breakthrough, intended to permanently replace insulin supplements from cows and pigs, resulted in widespread social anxiety about the ethics and harms of transgenic bacteria. However, simultaneously, many diabetics were experiencing severe immune reactions towards animal insulin as it differs to our own in a couple of amino acids. Due to the success of this new pharmaceutical replacement, the public quickly became more open to the uses of transgenic bacteria, and the science was soon being applied in many medical fields. We now use transgenics to create human growth hormones for those with growth deficiencies, clotting factors for haemophiliacs, and are also able to help dissolve blood clots in heart attack patients. Transgenic bacteria also have applications beyond the medical field, some are modified to produce ethanol, extract minerals and treat sewage. Bacteria have even been engineered to create biodegradable plastics.
Up until recently, genetic engineering had followed a specific traditional method called “recombinant DNA technology” as it involves combining DNA from different organisms. First discovered in 1979, this technology is still widely used today for many purposes, including the manufacture of insulin. The required gene must first be obtained either by automated synthesis, a polymerase chain reaction, or from the cell where it is being expressed. The enzyme reverse transcriptase catalyses the formation of a DNA strand complementary to the original mRNA strand which acts as a template. Primers and DNA polymerase enzymes are often added to convert this DNA into a double strand. Alternatively, a gene probe may be used to identify and locate a specific gene which can then be cut out using restriction enzymes. After the gene is obtained, it must be placed into a transitional vector. These are usually bacterial plasmids cut open by restriction enzymes at specific recognition sites. DNA ligase then catalyses the annealing of the required gene to the sticky end of the plasmid, which bind due to complementary base pairing. The recipient cell must then be encouraged to take up the recombinant plasmid either by electroporation, a high voltage disrupting the membrane, electrofusion, electric fields which help introduce DNA into cells, or by transfection, where the plasmid is inserted into a virus that transfects the host cell. However, the most common method of inserting the vector is by heat shock treatment which is used in the production of insulin. The bacteria, mixed with calcium chloride, are subjected to alternating heating and cooling periods which makes their walls porous by reducing repulsion between the plasmid and the host cell membrane. If a more immediate method of insertion is required, a ‘gene gun’ can be used. In industry, large quantities of recombinant bacteria are then cultured to produce insulin for healthcare.
Until recently, gene editing was extremely expensive, complicated, and took a long time to do. This has now changed with the application of “CRISPR”. CRISPR, a family of DNA sequences found within the genomes of bacteria and archaea, was discovered over 30 years ago in Japan, but the revolution only began in 2007 when the first experimental evidence that it was an adaptable immune system was published. If the old techniques of genetic manipulation were like a map, CRISPR is like a GPS system. With this discovery, the costs of modification shrunk overnight by 99% and became accessible to any individual with a lab. It used to take around a year to conduct an average genetic engineering experiment, and now that same experiment would only take two weeks. CRISPR’s mechanism is dependent on viruses called bacteriophages which attack and kill over 40% of ocean bacteria every day. Bacteriophages do this by inserting their own genes into the bacteria and taking over the organelles for their own survival and reproduction. Most of the time, bacteria fail to defend themselves against these viral attacks, however on the rare occasion when a bacterium does survive, it is able to activate CRISPR, its most effective antiviral system.
2019-3-24-1553420298