In 2019, a group of Spanish and Chinese biologists have reported their successful work in creating monkey-human hybrid “chimaeras” created by inserting human cells into monkey embryos in an effort to prove we can grow possible transplantable organs for humans in other species.
Also in China, geneticists have used similar techniques to place human brain genes in macaques, and early results indicate they are indeed smarter than their unaltered fellow monkeys.
And at the end of 2019, researcher He Jiankui was sentenced to three years in prison for using gene-editing techniques over a year prior to disabling some genes in the hopes of providing resistance to HIV infection in one of two human twin embryos, both of which were carried to the term: twin girls named Lulu and Nana. These children will go down in history as the first gene-edited humans.
The idea of manipulating the genome of living things goes back to the earliest examples of selective breeding in animals and plants, thousands of years ago. Though our ancestors didn’t realize it at the time, they were tinkering with the very fabric of what makes the biological world work. In essence, they were controlling evolution — that most powerful of natural feats.
When Mendel began to prop up this notion using the scientific method and his famous pea plant experiments, and an understanding of heredity blossomed, a new era of discovery was born. Unfortunately, some people — notably Hitler and his eugenicists — used this newfound knowledge to justify terrible acts.
Just as with our harnessing of other natural forces, like the ability to create alloys or start fission reactions, great goods and great dangers seem to come from all such advancements. Gene editing and the manipulation of DNA will be no different.
Humans have been performing genetic engineering in its most basic form since roughly 12,000 years ago with the advent of agriculture and animal husbandry, choosing which plants and animals would continue to live on via their seeds or offspring. Actual modification of DNA didn’t begin until the early 1970s, however, with the first methods practised on bacteria, plants and, ultimately, mice. Restriction enzymes were discovered that allowed scientists to “cut” DNA, while DNA ligase enzymes were used to join DNA strands. The advent of DNA sequencing gave us the power to actually read the genetic makeup of living things while using polymerase chain reactions let us generate copies of DNA segments.
By the mid-1990s, genetically modified bacteria were producing important drugs like insulin, grain and tobacco crops were modified to be more resistant to pests, and the Flavr Savr tomato became the first GMO food sold in supermarkets.
One of the second generations of gene editing tools, known as CRISPR/Cas9, is the most well-publicized and currently the easiest to utilize. CRISPR stands for “clustered regularly interspaced short palindromic repeats”, DNA sequences that were discovered in single-celled bacteria that actually help them recognize and destroy viral DNA when they are infected. Cas9 stands for “CRISPR-associated protein 9”, the enzyme CRISPR actually uses to detect the offending DNA. Scientists have repurposed this process and now use it to cut out and replace or add to a genome.
Though it was first discovered in the 1990s, CRISPR has undergone a long road of research to turn it into the highly effective solution it has become.
In 2017, a mutated, defective gene responsible for a debilitating and relatively common genetic disease called hypertrophic cardiomyopathy was “deleted” using the CRISPR tool by Oregon Health & Science University scientists from 54 viable human embryos. Thirty-six were completely cured of the defective gene, while most of the rest became partially free of mutations. Overall, their trial was a success, showing how useful CRISPR could be.
At this point, CRISPR/Cas9 could be used to target and remove specific mutations, but making large scale alterations is still difficult. Height has many genes that go into its determination, not to mention the environmental and nutritional factors that ultimately affect the result. Skin colour, seemingly so basic from a phenotypic standpoint, is actually tied to nearly 400 genes. Though scientists could theoretically make some of these large scale changes to a human embryo, the cost is prohibitive.
Beyond that, there are many ethical concerns. Editing the genes of a single individual would result in a person that is altered from what they inherited from their parents, but the changes would stop with them. However, the idea of germline editing — engineering the genes in the egg and sperm sex cells — would result in changes that would be heritable by the offspring of the individual/s that result from those sex cells.
Editing the germline, in effect, forever alters the species. If that altered individual procreates, his or her genes will be passed on to their children, and on and on. Because of the vast interplay between genes on so many traits, unforeseen consequences can arise from this. Without proper oversight and long-term validation of the tools, there will likely come a day when a biological disaster befalls one (or possibly many) species — and humans are at high risk of being affected. A Chinese scientist recently reported gene editing on babies that were brought to term.
In addition to the reports coming out of China, England’s Nuffield Council on Bioethics recently gave the greenlight to germline editing under certain conditions. This recommendation echoes one made by the National Academies of Science in 2017 in almost direct contravention with the same body’s conclusion two years prior that the technology was unduly risky. In other words, the apparently widespread concern that we will proceed with the technology before we truly understand the concomitant risks has already come to fruition in many ways.
Given some time — measured only in a few years to a couple of decades — some scientists, somewhere on Earth, will be able to genetically engineer physically superior athletes and soldiers. They may even be able to engineer those “perfect” people to also possess IQs >180, while also being born with immunities to most known diseases and cancers. Gene editing may even go so far as to allow forms of human to live on other worlds with gravity, atmospheric pressure, and chemical compositions of life and air too different for natural, un-engineered humans to survive. At some point, there will be multiple new “classes” of humanity based on the germline alterations made to their ancestors in the biological “wild west” of the 21st century.
Market research indicates that the business of genetics, specifically surrounding the use of CRISPR, will grow at a compound annual growth rate of over 32% between now and 2027. North America will likely be supplanted by Asia as the region with the greatest investments and profits generated from this new industry, with the types of companies benefiting being mostly biotech firms, pharmaceutical companies, research foundations and academic institutes. Design tools and Cas9 nuclease and gRNA are projected to be the uses that increase the most in that time. Some of the top companies using CRISPR technology now are Sigma-Aldrich, CRISPR Therapeutics AG, Horizon Discovery plc., and Editas Medicine.
We will need a comprehensive effort among the scientific and medical communities, politicians and bioethics professionals to plan for as many dangers as possible. It is assured that work will proceed in gene editing, both official and undocumented, and the best we can do is prepare for the ramifications.
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