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In the last several decades, genetic technologies have developed at an exponential speed and rapidly decreasing costs – meeting fantastically unprecedented levels of success. The last half-millennium, seeing the invention of the optical microscope by Janssen in 1595, the publication in 1859 of Darwin’s “On the Origin of Species”, and Mendel’s fundamental laws of inheritance in 1865, laid the foundation for Thomas H. Morgan to demonstrate in 1910 that genes were harbored in chromosomes, and Watson and Crick to detail the structure of DNA in 1953. Sanger and massively parallel sequencing of DNA were then invented in 1977 and 2000, respectively – leading up to the first human genome being sequenced on completion of the Human Genome Project, a 2004 crowning achievement, zenith of this buildup of genetic breakthroughs (1). The subsequent identification of over 20,000 human genes paved the way for exceptionally precise advances in human health (2): Since, upwards of 1,800 disease genes have been pegged and 2,000 genetic tests developed (1).
The genome era: A revolution in human health and identity
The rise of genetic sequencing and associated technologies in the last few decades has not only revolutionized healthcare, but laid the foundation for the new field of precision medicine – allowing for an unparalleled level of detail in reading, interpreting, editing, and writing genetic sequences.
A window of insight into our deep evolutionary history. Who are we and where do we come from? The DNA sequencing revolution has opened the floodgates to a more granular understanding of our deep evolutionary past in terms of our genetic lineages and migratory movements (3–5). Over 25 companies around the globe now offer direct-to-consumer services providing a consumer-controlled deep dive into heritage, identity and culture (6).
A leg-up for human genetic diagnostics. Further, genetic sequencing has enabled the detection of disease-causing mutations spanning large structural genomic rearrangements to modest, single nucleotide alterations – facilitating early, accurate molecular diagnoses. As a result, lives are at least improved and at best saved if a pre-approved medication can be administered targeting the specific molecular pathway found to be at play (7).
The success of classical gene therapy. Gene therapy has enabled the treatment of many diseases (8), altering disease-causing genes associated with diverse clinical pathologies and tissue targets. Among others, gene therapy for congenital vision loss (9), spinal muscular atrophy (10), hemophilia (11), Duchenne muscular dystrophy (12), and Batten disease (13) have been met with experimental and clinical success – providing astutely creative, relatively noninvasive treatments ingeniously targeting the core cause of otherwise cruel, devastating diseases.
Now, novel genetic editing methods are facilitating unparalleled levels of therapeutic precision and longevity. Capitalizing on the cut and paste mechanism of an ancient bacterial immune mechanism used to disarm invading pathogens, CRISPR (clustered regularly interspaced short palindromic repeats) has been the subject of well over 4,000 peer-reviewed scientific manuscripts yearly since 2018 (14) – truly revolutionizing human well-being at cellular, organism, population, and global scales.
The targeted correction of human genetic diseases. Gene editing therapies first entered clinical trials in 2010 as an approach to prevent HIV from infecting human immune cells (T cells) (15). Thereafter, CRISPR was successfully used to treat sickle cell disease and beta-thalassemia (16–18), remove a gene known to cause the severe, highly prevalent hypertrophic cardiomyopathy from one-cell embryo DNA (19), and inactivate the genetic mutation underlying Huntington’s disease (20,21).
Genetic editing as a cure for cancer. The power of CRISPR has been further applied to target the control center of cancer which stimulates abnormal growths: Its “cut-and-paste” mechanism was used to create a cancer-annihilating gene that shrinks tumors in mice harboring human prostate and liver cancer cells (22) – while in parallel being used to probe the cellular lineage and dynamics of cancers (23,24).
Genome editing and gene drives to eradicate infectious and other diseases. CRISPR genetic editing was used to snip out HIV from human immune cells (25), as well as eradicate mosquito-borne diseases such as dengue virus (26), while the spread of mosquitoes has been limited by hacking fertility genes (27). Finally, CRISPR has been used to make modified viruses that kill antibiotic-resistant bacteria (28) – taking on a whole new level of importance in light of the rising prevalence of antibiotic resistance (29) (which, as a sidenote, ironically results from the overuse of antibiotics in humans and farm animals, itself potentially preventable by a little genetic engineering genius (30,31)).
Genetic technologies for reproductive biology. Genetic technologies have galvanized the field of assisted reproduction, opening the door to in vitro fertilization (IVF) and revolutionizing reproductive decision-making. From prenatal and preimplantation genetic testing to somatic and germline gene editing in the future, genetic innovations will continue to deeply support human reproduction in astonishing ways (32,33).
Genetic editing as a powerful tool for functional genomics and synthetic biology. Finally, beyond its direct clinical applications, genetic editing has tremendous theoretical potential, allowing for a unique method to dissect molecular pathways and biological processes – of mouthwatering utility in light of the unknown function of up to 30% of human genes (roughly 6,000 of 20,000) (34,35). Further, annotating the yet undiscovered “dark matter” of the genome will also forge whole new areas of disease biology and therapeutic targets (36), while associated progress in synthetic biology will advance broad biological insights and drug discovery and production (37).
In light of the 19+ million cancer-related deaths globally in 2020 (38), 1.5 million new HIV infections in 2020 (39), genetic defects estimated to be present in at least 10 percent of all adults (40), and an estimated increase in female infertility of up to 15% in the past two decades (41), advanced genetic technologies not only represent a beacon of hope enabling the better understanding of many afflictions, but a medical and moral imperative with the potential to improve millions of human lives on a yearly basis.
Genetic innovations for biodiversity protection and environmental sustainability
Genetic engineering for agricultural improvements. Naturally, CRISPR’s reach extends to all animals, including livestock (42,43) – improving reproductive traits, conferring resistance to infectious disease, and generating animal models for biomedical research (44). Applications to disease resistance are particularly gaining prominence (45), and virus-free pigs were successfully created in 2017 (46). CRISPR may also enhance crops by modifying their appearance, taste, and nutritional components (47,48), such as in the production or low-gluten wheat (49) or highly nutritious rice (50) – contributing to building robust, sustainable food systems.
Genetic engineering for the preservation of biodiversity. Finally, genetic engineering has been leveraged to edit the genomes of key extinct or endangered species in order to preserve life in all its most diverse forms – of particular salience in light of the consequential decline in genetic diversity resulting from heavy human activity-induced bottlenecks (51,52) resulting in many species rapidly brushing up against extinction (53).
The flirtatious tango of Biomedicine and Ethics: A conscientious history
The term “bioethics” emerged in the 1970s, coined by the biochemist Van Rensselaer Potter to describe an ethics of biomedicine (55), and Warren Reich’s 1978 Encyclopedia of Bioethics was the first to describe this concern of philosophers, lawyers, sociologists, clinicians and scientists with “the systematic study of human conduct in the area of the life sciences and health care” (54). Recently, the field of bioethics has appropriately skyrocketed in response to rapidly evolving biomedical technologies – in 1991, the International Association of Bioethics was founded, and the fifteenth World Congress of Bioethics was held in 2020. The first nine of the fifteen articles of the Universal Declaration on Bioethics and Human Rights, adopted by the United Nations Educational, Scientific and Cultural Organization (UNESCO) in 2005, cover key guiding principles and broad social dimensions of bioethics (56), while the World Health Organization (WHO) has set forth a framework for governance and guidelines on human genome editing (57,58). In parallel, an international effort led by the U.S., United Kingdom, and China is harmonizing the regulation of genome editing technologies (59), while the U.S. Defense Advanced Research Projects Agency (DARPA) has invested $65 million in a project on “safe genes” designed to continue to fully ensure the accuracy and safety of CRISPR editing techniques (60).
As well-guided as they are, in the end, genetic technologies capitalize on inherently natural, ancient evolutionary mechanisms (61), reflect a profound understanding of their underlying molecular biology, and are increasingly specific and predictable in their applications – earning their spot as a stunning well-controlled, high-specificity pillar of modern medicine (62,63).
The unprecedented promise of genetics – an optimistic outlook
Genetic technologies have reached an inflection point, allowing for unprecedented levels of control over the web of human, faunal, and floral life. As creative and fascinating as they are profoundly revolutionary in their scope, these technologies form the most exciting and promising area of contemporary biotechnology: Let’s keep embracing them with wisdom and vision as we continue to improve the human condition and preserve Life in all its most diverse forms into the future.
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