Go back in time to the late 19th century and imagine yourself being told that in a couple of decades, the internet and smartphones would take over your life and revolutionize the way you live. You would have laughed at such a claim; but now, it is a reality…a breakthrough of immense magnitude which, without a doubt, surpassed everybody’s expectations of what a short period of time could bring about in terms of technological progress. Science fiction is no longer a fantasy, and we very often do not think about it. The case is no different with genetic engineering. Many students all around the world have at least heard of these terms, either in advanced Biology high school classes or in Genetics and Biotechnology courses in university. But what is it truly about in the real world, and where does it stand in the field of medicine?
A Brief History of Genetic Engineering
Humans have been engineering life for over 300,000 years. They have altered the genetics of not only bacteria so that it produces prescribable drugs but of other multicellular organisms as well, yielding see-through frogs, featherless chicken, and fluorescent zebrafish. Over time, genetically modified organisms (GMO’s) have stolen the spotlight. According to an article by Gabriel Rangel published in the Harvard Medical School blog, governments worldwide have supported and continue to move forward with genetic engineering (GE) research, setting in motion a new era of genetic medicine. But what is genetic engineering, the so-called recombinant DNA technology, all about? The process is pretty simple for scientists to understand; and the secret ingredient is the code of life–DNA, which is more formally known as Deoxyribonucleic acid. This complex molecule guides the growth, function, development, and reproduction of everything alive on this Earth, with innumerable information and instructions encoded in its structure. Therefore, changing the DNA composition changes the organism carrying it. This is the core principle of genomic editing and is actually rooted in the “Central Dogma of Biology,” which dates back to 1958, the year scientist Francis Crick discovered the structure of DNA. In brief, the central dogma is the “process by which the instructions in DNA are converted into a functional product.” With that being said, recombinant DNA (rDNA) technology involves several techniques used to cut, copy, and paste pieces of genetic material between different biological species, resulting in hybrid DNA which can be introduced into an organism, giving rise to a new combination of genetic information (hence the name recombinant). For this to happen, genes contained within the DNA must firstly be prepared, either by naturally occurring enzymes that cut large chunks of DNA into smaller insertable ones at specific loci or artificially in a laboratory setting with the help of reverse transcriptase, an enzyme that can make DNA by using messenger RNA as a template. After this starting step is successful, the products can be inserted into the host cell/organism where these insertions are to be expressed. In simpler terms, the genetic code is translated into a respectful coded protein, the functional unit. By doing so, a desired trait has been bestowed upon the recipient. “These new ideas have influenced all kinds of biological work,” says the British Medical Journal.
Genetic Engineering And Pharmaceuticals: Paving the Way to Disease Treatment
After Boyer and Cohen developed the solid grounds of modern genetic engineering in 1973, Jaenisch and Mintz then created the first genetically engineered mouse just 10 years after, paving the way for rapid advancements in the field. Interestingly, in 1982 the FDA approved the first biotechnology pharmaceutical, Humulin made by inserting human genes responsible for insulin production into E. Coli bacteria, making the latter a source of insulin production by itself. After several FDA clinical trials exceeding 400 patients, this genetically engineered drug has proven effective and is utilized by more than four million users suffering from diabetes every day. Moreover, because this technique succeeds in mass production of insulin, Humulin is expected to alleviate the shortage of diabetes-treating-drugs predicted within the next ten years. In addition, this GE artificial insulin is available in both a vial and disposable prefilled pen, hence offering practicality and convenience among its buyers in terms of how it can be administered. From biotech companies such as Genentech in the United States to others like Biocon Ltd in India, researchers continue to praise recombinant DNA (rDNA) practices in hopes of achieving more improvements and diversifying the types of drugs the technology could offer.
Dr. D Denner of Eli Lilly pharmaceutical company headquartered in the American state of Indiana, views insulin production by genetic engineering as the start of a long path toward developing many other hormones and even maybe new antibiotics. One of the most heard of hormones is HGH (Human Growth Hormone), secreted by the pea sized organ near our brain–the pituitary gland–influences our height, helps build bones and muscles, etc. Individuals with pituitary and growth disorders are often treated by supplementing them with HGH, but the challenge here is that the only source of it is humans. Previously, the pituitary glands of cadavers were gathered and used for this purpose for over 20 years until the U.S. Food and Drug Administration stopped all distribution of cadaver-derived hormones in 1985 after tens of people died due to contaminated HGH. It turns out that a cadaver was infected with Creutzfeldt-Jakob disease, CJD, resulting in rapid brain degeneration upon use. Luckily, genetic engineering is here to solve the issue and offer an alternative. Biotech companies have been working on bacteria, into which they have been inserting HGH-producing genes to produce transgenics capable of pumping HGH contamination-free. The widely used source of growth hormone used for decades has now become Genentech’s FDA approved genetically engineered HGH, Protropin. The latter is known to be the second recombinant drug sold in the U.S. after the beforementioned engineered insulin pharmaceutical, Humulin. Safe in treating children with growth disorders, the increase in its supply has also prompted its infiltration into the sports domain, bettering the performance of athletes as well. Studies have shown that many other recombinant proteins are also available due to DNA technology, such as follicle stimulating hormones (FSH). It is worthy to note that there exists advantages of employing genetic modifications to proteins over chemical alterations: not only are GE products biocompatible and biodegradable, but also do not contain harsh chemicals whose byproducts are very often carcinogenic.
Another example of the success of genetic engineering is with hemophiliacs who suffer from a deficiency in blood clotting factors, which can be healed via recombinant coagulation factors. Unlike past methods of extraction from pooled human blood which increase transmission of viruses like HIV and hepatitis C from donors to recipients suffering from hemophilia, genetic engineering has eliminated this problem. The reverse is also true: patients suffering from blood circulation and heart disease also benefit from genetically engineered proteins. Tissue Plasminogen Activator (TPA), a blood protein that dissolves blood clots can also be microbially engineered and has become widely used in hospitals across the United States where heart disease is the leading cause of death.
While drugs and proteins were impressive achievements of GE, great accomplishments in the field were on their way and so it happened when recombinant vaccines kicked through. The way they work is the following: a small piece of DNA taken from the virus is inserted into the manufacturing cells, such as yeast. These cells then produce one of the surface proteins of the virus, which is then purified and used as the active ingredient in the vaccine. With that being said, a few of the many proteins of the antigen (a scientific term for a biological “enemy”) is used in the vaccine because otherwise, that would be detrimental to the host cell which might not be able to mount an immune response had the antigen been complete. Therefore, the purified protein which is the “foreigner” is the entity recognized by our immune system and is enough to trigger a response that can protect against the disease. In the UK alone, some examples of recombinant vaccines are the Hepatitis B vaccine, HPV vaccine, and MenB vaccine.
Genetic Engineering: A Look Into The Future
Yet, when speaking of genetic engineering, the first thought that comes to mind is that of pregnancy and designer babies. While the FDA has approved trials to treat blindness, cancer, and sickle cell disease in humans using gene editing, “the treatment of diseases in fetuses poses the next frontier,” says Eve Glicksman, a health and science writer for the Washington Post. Fixing a baby’s abnormal genes may soon be possible, yet for the meantime, the field of medicine remains the seat of continuous controversy and debate around this topic in the domain of genetic engineering. While it carries substantial ethical and medical concerns, He Jiankui, a Chinese scientist took initiative and edited twin embryos to disable a gene called CCR5 in hopes of avoiding transmission of HIV from their father. Per Jiankui, the procedure was proven possible, and the twins were “born normal and healthy”. Although professor Jiankui’s claims have not been totally verified, a larger scale project was carried out just one year later with rats that had HIV in all of their cells, and interestingly, similar genetic engineering techniques succeeded in removing more than 50% of the virus from cells all over the body. With Russian scientist, Denis Rebrikov, also moving forth in his plans to disable the same gene in embryos to be implanted in HIV-positive mothers, it seems prenatal genomic editing is not that far-fetched. Advocates for such alterations argue that by genetic intervention, parents now have a third option to choose: they do not have to terminate a pregnancy they deem unfortunate nor birth a child who will most likely face medical challenges; they can instead bring to life a being that is normal and prepared for the world’s endeavors.
For instance, suppose a woman visits a genetic counselor and learns that her fetus suffers from the genetic disease Angelman syndrome, characterized by intellectual and speech impairment, epilepsy, and a minimized head. Medicine still does not know of any treatment for the syndrome except resorting to genetic engineering. Scientists from the University of North Carolina have treated Angelman syndrome in fetal mice by reactivating the mutated gene of wild-type counterparts. “The therapy has also proven effective in cultured brain cells,” studies have shown. Bret Asbury, law professor and associate dean in Drexel University, is currently exploring the ethical implications that fetal genetic abnormalities have on pregnant mothers and their families. “There are no easy answers to the many questions that will arise in this space,” he claims. It is evident therefore that a mother must take a life-changing decision when deciding the fate of pregnancy, and in such a scenario, it is imperative that she weighs the potential risks of gene therapy with its pros. Such as in the case of Angelman syndrome, she is also bombarded by a spiral of ethical concerns; the fetus may either enter the world healthy or suffer from infection and brain damage, even possibly miscarriage. Gene editing might also cause off-target changes whereby genes other than the intended one are altered, possibly resulting in even greater repercussions.
What is known about genetic engineering in medicine is just a grain of salt. Just like all advancements known to mankind, GE is another ticking time-bomb of promising achievements waiting to explode. Considering the various benefits and consequences genetic engineering presents, whether such technologies must be praised or feared constitutes the foundation of its controversial nature. Will gene editing alleviate man’s sufferings and cure his diseases? As
technology advances, more and more people may argue that not using genetic modification is the wrong choice. If you can make your offspring immune to Huntington’s disease, why not also give him/her an enhanced cardiovascular system? Why not prevent hair loss or even possibly end the problem of aging? With genes directly related to age, genetic engineering could stop, slow down, and even maybe reverse it. Why not live another century or maybe forever if we want to? These obstacles are enormous and might be too big for our planet to handle. As powerful as genetic engineering may seem, scenarios like these are far, far off into the future, if they ever become possible at all. When Darwin wrote about evolution in 1859, did he foresee genetic engineering as a step in our progress as a species in this universe? Time will tell.
Edited by Mohamad Wehbe