CRISPR: Specter or Savior?

Raavee TripathiMay 24, 2021Life and DeathFeatures
CRISPR: Specter or Savior?

Artwork by Dottie Young

In late 1999, when Adam Nash was just an embryo in a dish, scientists tested his DNA to check for genetic markers of Fanconi-anemia, a rare genetic blood disease from which his sister suffered.

They also checked for a gene that would reveal whether the siblings shared the same tissue type. His sister, Molly, needed a donor match for stem cell transplantation, and Adam was conceived in vitro so that the stem cells in his umbilical cord could be utilized for the transplant.

While this sounds like a warped version of "My Sister's Keeper", Adam’s birth ushered in a new era in medicine, bioethics, and life and death. Adam is considered the first 'designer baby' and a notable example of preimplantation genetic diagnosis. Just a couple of years ago, genetic engineering sounded like the stuff of science fiction novels. However, it is now becoming a part of normal life, from making tomatoes juicier to giving people like Molly a new lease on life.

We went from valiantly venturing beyond the ‘edges’ of the Earth to discover new continents to leaving our footprints on the moon. When seeds are being modified to produce taller, healthier, pest-resistant plants, is it so far-fetched that we can modify human babies too? When would it become appropriate to cross the line between life preservation and just choosing desirable characteristics? Most importantly, what then stops the creation of the biologically elite?

Still, it could be that we never have to worry about such issues, since certain things seem to simply lie out of the grasp of science. The very idea sounds rather ridiculous — a couple customizing their ‘designer baby’ much like you would a t-shirt.

A google search for the term 'designer baby' yields quite a few results ranging from the latest maternity fashion to debates on humans playing god. Actually, it refers to a baby that has been given certain traits, such as disease resistance, through genetic engineering. Scientists or doctors can ensure such desirable traits by either selecting an embryo displaying favorable genes or genetically modifying the embryo.

Preimplantation genetic diagnosis, or PGD, is the testing of embryos for gene defects. An array of embryos are analyzed, and one with the desired genetic makeup is selected for implantation and pregnancy.

For example, an individual with Huntington's disease might wish to have a child that will not suffer from the same illness. Huntington's disease is a progressive brain disorder in which nerve cells break down over time. Most importantly, Huntington's is a mendelian disorder, which means that it has a single causative gene. First, several embryos are prepared and genetically tested. The embryo not exhibiting the gene for Huntington's is used for the pregnancy. This process ensures that the child will not carry the gene for Huntington's.

Germline engineering, or genetic modification, is another method of altering a baby's genetic information before birth such that the change becomes heritable thereafter. The desired genetic material is introduced into the embryo itself or to the sperm and/or egg cells, either by delivering the selected genes directly into the cells or using gene-editing technology.

The most commonly used gene-editing technology is referred to as "CRISPR". Simply put, scientists use a small strand of RNA to direct the Cas9 enzyme to a site in the DNA with a similar sequence. The enzyme then cuts both strands of DNA at that site, inserts new genetic information, and then allows cellular repair systems to heal the gap. This technology is relatively cheap and widely available, making it immensely potent. However, problems arise when there are no restrictions imposed.

In 2018, He Jiankui, a Chinese biophysicist, sent shockwaves through the world when he announced that he had successfully used CRISPR to make the first-ever genetically modified babies. He edited the CCR5 gene in two embryos to make the babies resistant to HIV.

Jiankui faced severe backlash from around the world for myriad reasons. His experiment took place in absolute secrecy, and with forged authorization since genetically modifying human embryos was illegal in China and worldwide. Additionally, it completely disregarded widely accepted standards of bioethics.

Why do bioethicists worldwide insist on imposing restrictions, when both PGD and germline engineering offer such outstanding benefits?

Part of the answer lies in the mechanism behind CRISPR, which relies on the cell's inherent ability to perform repairs. The mechanism used is error-prone and can insert or delete a small number of DNA letters. If the cell is provided with a new DNA 'template', the cell may use that template sequence to mend the cut, resulting in a true genetic rewrite. However, this is only an ideal situation.

Cells’ repair processes are known to be unpredictable, so favorably editing a gene is a gamble. Additionally, Cas9 and other enzymes have been known to cut DNA at non-targeted sites too, especially when there are multiple DNA sequences in the genome similar to the target sequence. Such off-target cuts may result in severe health problems. For example, an edit targeted to mitigate tumor growth/formation may end up causing cancer.

Due to such issues, genetic modification has been tested only on mice, which contributes to the uncertainty. Error rates may vary between human and mice cells, so findings are less helpful.

Most significantly, in the words of Dutch researcher Cecile Janssens, "Research shows that geneticists cannot read the genetic code and know who will be above average in intelligence and athleticism. Such traits and diseases that result from multiple genes and lifestyle factors cannot be predicted using just DNA, and cannot be designed. Not now. And very unlikely ever."

DNA variations are changes in genetic code that increase the likelihood of an individual showing certain traits. These variants do not decisively determine a trait, such as intelligence, but increase its likelihood, along with other factors such as upbringing and lifestyle. To be able to ensure increased intelligence in babies, scientists would have to make several genetic modifications and carefully control conditions.

This uncertainty also extends to attempts at disease prevention. For example, mutations in the BRCA gene substantially increase the risk of breast and ovarian cancer. Selecting embryos that do not have these mutations removes the primary cause of the disease. However, women who do not have the BRCA mutations can still develop breast cancer due to other factors, like all women.

Hence, biological constraints, not technological ones, limit the creation of designer babies. The origins of common traits and diseases are too complex and intertwined to modify the DNA without introducing unwanted effects. When there is such a rift between theory and actuality, is it not unethical to use the technology and promise certain results?

Jiankui chose to flout such ethical norms, perhaps to revolutionize gene editing and jolt the scientific community. He disabled the CCR5 gene, creating a mutation seen naturally in around 10% of Europeans, that provides them with immunity against HIV. However, the CCR5 gene contributes to immunity against the West Nile virus, and Jiankui might have compromised this immunity in his subjects. More importantly, CCR5 has been shown to play a role in cognitive function; mice with the CCR5 gene disabled were found to have enhanced learning and memory.

From an ethical viewpoint, Jiankui's experiment and the rationale behind it appear severely flawed. Geneticist Eric Topol said, "This [experiment] is far too premature ... We're dealing with the operating instructions of a human being. It's a big deal."

The specter of a harsh, impersonal, and authoritarian dystopia always looms in these discussions of reproductive control and selection. Novelist Kazuo Ishiguro warned that “we’re coming close to the point where we can, objectively in some sense, create people who are superior to others” thanks to advances in gene editing.

The science fiction film Gattaca depicts a world in which only genetically modified individuals can engage in the upper strata of society. Opponents of the concept of 'designer babies' argue that if this technology becomes an accessible medical practice, then it will create a division between those who can afford it and those who cannot. Such biological, social, and absolute division would only strengthen pre-existing economic gaps.

In addition to cost barriers, some groups and cultures attach a stigma to infertility and genetic disorders, and this stigma can reduce public awareness of genetic testing and modification or willingness to face social backlash after undergoing such treatments.

In India, using techniques such as amniocentesis, there is a selective abortion practice targeting female fetuses. Before extensive interventions, certain regions showed shockingly skewed gender ratios, such as in Haryana, where there used to be only 831 females for every 1,000 males. With germline engineering and PGD, it will become easier to produce culturally 'desirable' male children without having to 'dirty hands' with selective abortion practices. How then will maintaining a balanced sex ratio be policed?

Some argue that individuals choosing to undergo such gene therapies do not hold the right to make these choices for future generations without their consent. Other bioethicists say that parents hold a right to prenatal autonomy since they already possess a high degree of control over the outcome of their children’s lives in the form of upbringing. They suggest that it may not be all that different from choosing when to have a child or using contraception.

In our era of utilitarianism and the individual’s absolute right to choose, when is it proper for governments to coerce or prohibit people from making particular choices, such as not eliminating the gene for a disability? What if a hearing-impaired couple doesn't want to eliminate the gene for hearing loss?

Gene editing in humans remains highly questionable. This technology isn't perfected, and it could be many decades before it can be used without adverse health effects for individuals and society. But when the suffering of so many people living with diseases like cystic fibrosis and Huntington's could be averted, the decision to delay such research cannot be taken lightly. As long as the research is delayed, lives are lost every day.

Going down that slippery slope will allow science, not nature, to guide evolution and societal change. However, when have humans ever shied away from taking their destinies into their own hands?

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Raavee Tripathi is a seventh grader at Riverside School in Ahmedabad, India. She enjoys dancing, reading dystopian books, debating, playing sports, and just surfing the internet. Her ambitions do change, but her current goal seems to be re-reading the Harry Potter series for the 15th time.