By Suhani Khandelwal
Published 10:56 PM EST, Sun March 21, 2021
Genetic engineering is the process of using recombinant DNA (rDNA) technology to alter the genetic makeup of an organism. Conventionally, humans have manipulated genomes indirectly by controlling breeding and selecting offspring with desired traits. Genetic engineering involves the direct manipulation of one or more genes. Most often, a gene from another species is added to an organism’s genome to give it the desired phenotype.
Recombinant DNA technology started with pretty simple things like cloning very small pieces of DNA and growing them into bacteria and has now evolved into a massive field where whole genomes can be cloned and moved from cell to cell, to cell-using variations of techniques that all would come under genetic engineering as a very broad definition.
New genetic technologies are exhilarating and terrifying. Society might successfully overcome diseases by tweaking individual genomes or selecting specific embryos to avoid health problems. But it may also give rise to “super-humans” who are optimized for certain characteristics (like intelligence or looks) and exacerbate inequalities and extreme discrimination in society.
How It’s Done: CRISPR
CRISPR (pronounced “crisper”) is shorthand for “CRISPR-Cas9.” CRISPRs are specialized stretches of DNA. The protein Cas9 (or “CRISPR-associated”) is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA.
CRISPR technology is a simple yet powerful tool for editing genomes. It allows researchers to easily alter DNA sequences and modify gene function. Its many potential applications include correcting genetic defects, treating and preventing the spread of diseases, and improving crops. However, its future of great promise also raises ethical concerns.
CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea (the domain of single-celled microorganisms). These organisms use CRISPR-derived RNA and various Cas proteins, including Cas9, to foil attacks by viruses and other foreign bodies. They do so mainly by chopping up and destroying the DNA of a foreign invader. When these components are transferred into other more complex organisms, it allows for the manipulation of genes, or “editing.”
The First Genetically Engineered Human Babies
He Jiankui became widely known in November 2018 after he had claimed that he had created the first human genetically edited babies, twin girls known by their pseudonyms, Lulu and Nana. The announcement in November 2018 of Lulu and Nana, who were born healthy by mid-October 2018, was initially praised in the press as a major scientific advancement. But following scrutiny on how the experiment was executed, He Jiankui received widespread condemnation.
He announced that he had modified a key gene in a number of human embryos in a way alleged to confer resistance to HIV. The modification might be passed on to the offspring of children born with it. He recruited couples in which the father was infected with HIV and the mother was not. In a talk at the International Summit on Human Genome Editing in Hong Kong, China, He said he wanted to spare the babies the possibility of becoming infected with HIV later in life. The technique could be used to reduce the HIV/AIDS disease burden in much of Africa, he argued, where those infected often face severe discrimination.
This news a couple of years ago shocked the world. But although this use of advanced technology to change the human gene pool was premature, it was an indication of how genetic science will alter our healthcare, the way we make babies, the nature of the babies we make, and, ultimately, our sense of who and what we are as a species.
This shift in our healthcare will ensure that millions of people will have their genomes sequenced as the foundation of their treatment.
These huge datasets of genetic and life information will then make it possible to go far beyond the simple genetic analysis of today and to understand far more complex human diseases and traits influenced by thousands of genes. Our understanding of this complex genetic system within the vaster ecosystem of our bodies and the environment around us will transform healthcare for the better and help us cure dreadful diseases that have plagued our ancestors for centuries.
But as revolutionary as this challenge will be for medicine, the healthcare applications of the genetics revolution are merely stations along the way to the ultimate destination – a deep and fundamental transformation of our evolutionary trajectory as a species.
As the genetic and health data pools grow, analysis of large numbers of sequenced genomes will make it possible to apply big data analytics to predict some very complex genetic disease risks and the genetic components of traits like height, IQ, temperament, and personality style with increasing accuracy. This process is what we call “polygenic scoring.”
The most profound application of all this will be in our reproduction of progeny or “baby-making.” Before making a decision about which of the fertilized eggs to the implant, women undergoing in vitro fertilization (IVF) will be able to decide to have a small number of cells extracted from their pre-implanted embryos and sequenced. With CRISPR and other advanced technology, this can be used to screen for single-gene mutation diseases and other relatively simple disorders. Polygenic scoring, however, will soon make it possible to screen these early-stage pre-implanted embryos to assess their risk of complex genetic diseases and even to make predictions about the heritable parts of complex human traits. The most intimate elements of being human will start feeling like high-pressure choices needing to be made by parents.
Adult stem cell technologies will then likely make it possible to generate hundreds or thousands of a woman’s own eggs from her blood sample or a skin graft. This would open the doors of reproductive possibility and allow parents to choose embryos with exceptional potential capabilities from a much larger set of options.
The complexity of human biology will obviously place certain limits to the extent of possible gene edits that can be made to these embryos, but all of biology, including our own, is extremely flexible. How else could have all the diversity of life today emerged from a single cell nearly four billion years ago? The limit of our imagination will become the most substantial barrier to our re-forming biology.
The same tools that will help cure our worst sicknesses, save our children, extend our lifespan, allow us to live healthier, more robust lives will also open the door to inevitable exploitation. Prospective parents with the best of intentions or governments with negligent regulatory structures or aggressive ideas of how population-wide genetic engineering should be used to enhance national competitiveness or achieve some other goal could drive us into a genetic arms race that could undermine our essential diversity, dangerously divide societies, lead to dangerous, destabilizing, and potentially even deadly conflicts between us, and threaten our very humanity.
Suhani Khandelwal, Youth Medical Journal 2021