CRISPR Myth #1: Creating the “Designer Babies”

There are a lot of myths surrounding the gene editing field. As science advances, and we gain more insight into the human genome, we become capable of pushing technological boundaries. With CRISPR being a powerful tool designed for the precise editing of the genes, currently used for the production of therapeutic treatments and the engineering of improved plant varieties, the questions regarding the possibilities of “designer babies” arise. Is it really possible to customise physical traits of future generations? Are we heading towards the edited version of humanity? Let’s try to distinguish between science fiction and reality.

GMO vs Gene Editing

As I am writing this, I’m looking up news articles and social media posts made about “Designer Babies”, who are sometimes referred to as “GMO babies” or “GM babies”. Let’s get the first thing out of the way: gene editing and GMO (genetically modified organism) are different things. GMO is not a bad thing, but it is important to differentiate between the two terms in this discussion.

GMO and gene editing are both techniques used to alter the genetic makeup of organisms, but they differ significantly in their methods and outcomes. GMOs typically involve the introduction of foreign DNA from a different species into an organism’s genome, creating transgenic organisms with new traits (1). This process often involves the use of traditional genetic engineering techniques like recombinant DNA technology (1). Golden rice is the golden standard of a genetically modified crop. The scientists took the genome of rice and put two beta-carotene biosynthesis genes, psy from daffodil and crtl from a soil bacterium, into it (2). As a result, golden rice can produce more beta-carotene, a precursor of vitamin A (2). The intent behind golden rice is to be grown and consumed in areas with a high vitamin A deficiency: a disease that yearly leaves between 250,000–500,000 children worldwide blind, and is fatal in up to half of the cases.

While we are on this topic, Greenpeace recently blocked the planting of golden rice in the Philippines: it can lead to tens of thousands of children dying from vitamin A deficiency which was going to be prevented (3). And that is the price of GMO scare.

Gene editing, particularly with tools like CRISPR, allows for precise modifications within an organism’s own DNA without necessarily introducing foreign genes. Gene editing can add, delete, or modify specific genetic sequences directly, resulting in changes that could also occur naturally. CRISPR-based modifications, in general, do not fall under GMO regulations as they are not introducing new genes to the target genomes to obtain the desired traits (4).

So a GMO baby would be made if we, for example, insert a gene from a jellyfish that causes bioluminescence into an embryo’s genome to make the baby glow in the dark. And if we edit the genome to eliminate a mutation in the CFTR gene that causes cystic fibrosis, we would have a genetically edited baby. The phrase “GMO/GM baby” implies the former.

The complexity of human traits

It is a common misconception that human traits are dictated by single genes. Human traits, particularly those like intelligence, physical appearance, and athletic ability are polygenic, meaning they are influenced by many different genes, each contributing a small effect. For example, intelligence is estimated to be influenced by over 500 genes, each playing a minor role in cognitive abilities (5). Intelligence is, however, not just hereditary, but is also shaped by environmental factors, such as upbringing, education, social interactions, and nutrition. Physical traits like eye and skin colour also are not governed by just one gene: simply take a look around to notice the variation in phenotypes. From the latest study I could find on hair colour genetics, more than a hundred genes are involved (6). To alter one trait, you may need to edit hundreds of genes. To create a designer baby with selected traits — tens of thousands of genes. To put it simple: you will not be able to do that. Not any time soon, anyhow.

This genetic complexity is a significant challenge for CRISPR. Even if we could identify all the genetic variants associated with a particular trait (which we currently cannot do with 100% certainty), editing them with the required precision would be extremely difficult. The interactions between these genes are not fully understood, and altering one gene might have unintended consequences on other genes.

Let’s look into human eye colour, a trait that has “only” 16 genes associated with its inheritance (7). OCA2 and HERC2 are the main genes that were found to be associated with eye colour variation (7). Let’s edit OCA2, a gene that encodes P protein. Unfortunately, as of now, the exact function of the P protein is unknown (so the consequences of the editing will be unpredictable), but this protein is thought to be involved in the production of melanin (8). Melanin gives colour to eyes, skin, and hair, and plays a role in normal vision (8). Mutations in the OCA2 gene cause albinism, which unfortunately significantly increases risk for sun-induced skin-cancers (9). And then HERC2 gene: the mutation in this gene is common to nearly all people with blue eyes. Yey! Mutations in HERC2 gene are also associated with leukemia, breast cancer, melanomas, gastric and colorectal carcinomas, as well as neurodevelopment disorders, causing cognitive delay, seizures, speech disorders, and ataxia (10). Furthermore, HERC2 gene is involved in cell cycle regulation, DNA repair functions, embryonic development, mitochondrial function, and motor coordination (11). Assuming that we can be 100% certain where to cut the gene (and for this gene we can’t, for now), there is still a risk of off-targeting. The trade-off between your kid having blue eyes and having issues described above would not be worth it (I hope). Now imagine you still have 14 more genes that influence eye colour. And we don’t even consider epigenetics modifications here…

Image from “The Designer Baby Distraction” that shows publication covers with “edited babies” https://asm.org/articles/cultures-magazine/volume-4,-issue-4-2017/the-designer-baby-distraction

CRISPR and its limitations

CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats, is a gene-editing technology that allows to modify DNA with high precision. By using a guide RNA (gRNA) to target specific sequences in the genome and a Cas9 protein to cut the DNA, CRISPR can introduce changes at precise locations.

However, the idea that we can now “engineer the human race” or “edit humanity” using CRISPR is a significant oversimplification. A bit misleading, too.

CRISPR does allow multiple genes to be edited simultaneously in a process known as multiplexing. The number of genes that can be edited at once depends on several factors, such as the design of CRISPR system, the efficiency of the delivery method, and the cell type being targeted. For a single human cell, the highest number (that I found) of genes edited simultaneously was ten (12). It is significantly lower than what we would need to “edit humanity”, it would not even be enough for eye colour. To edit 16 genes, you would need 16 different gRNAs (or 32, depending on the system you are using), each specifically designed to target a unique gene. Designing them would already be troublesome — you need to ensure that they are unique to only the sequence you want to cut, nowhere else. The activity and specificity of gRNAs can be unpredictable, and mismatches between gRNAs and target size result in off-target effects. Then you have to deliver the CRISPR components to the cell. All delivery methods have limitations in how much material they can carry and effectively introduce into cells. Delivering even 16 gRNAs simultaneously will stretch the current capabilities of delivering systems.

Assuming we manage to deliver these 16 gRNAs into the cell, there are still further problems. The more genes you target, the higher the likelihood of off-target effects, where CRISPR cuts DNA at unintended sites. These off-target cuts could introduce mutations elsewhere in the genome, potentially leading to harmful and unpredictable consequences. Even if there is no off-targeting, editing multiple genes could lead to genomic instability, where too many breaks in the DNA could overload the cell’s repair mechanisms, leading to errors in repair and potentially compromising the cell’s viability or function. And then, of course, the fact that genes do not function in isolation — they interact with each other in complex networks. Editing 16 eye-colour-genes could disrupt these interactions and, considering that a lot of genes have more than one function, it could lead to unforeseen consequences. The risk of interfering with essential pathways increases with the number of edits, which could result in developmental abnormalities or non-viable embryos. As a response to the extensive editing, the embryo might trigger apoptosis (programmed cell death) to prevent successful development. Our cells are smart.

Most successful applications of CRISPR focus on editing one or very few genes at a time, particularly in therapeutic contexts, to minimize risks and maximize precision. Recently approved Casgevy, a gene therapy treatment for patients with sickle cell disease, target one gene — BCL11A (13). The treatment for the inherited retinal disorder Leber congenital amaurosis (LCA) also targets one gene — CEP290 (14). Additionally, such use of CRISPR does not create heritable modifications.

Then what about using CRISPR editing to prevent serious genetic diseases in the embryos? Using CRISPR to prevent children from having inherited blindness is completely different from using technology to alter eye colour. Still morally questionable and currently prohibited by laws of most countries, but at least more possible. Personally, even if it is allowed in the future, I don’t think it will become a common practice. Genetic screening of embryos produced by in vitro fertilization (IVF) already allows checking for non-affected embryos, if the parents are known to carry genetic mutations. It would be hard to justify the need to genetically edit embryos with CRISPR, considering all the risks and possible consequences.

Ethics and awareness

Germline engineering is the process in which the genome of an individual is edited, and the changes become heritable. As of today, no country explicitly permits germline engineering on embryos that will be carried to term (15). A lot of countries have laws prohibiting it altogether (15).

We don’t know what the long-term effects might be, and it would be unethical to check. Genes interact in complex ways that we don’t fully understand yet. Changing such genes could lead to unexpected health problems or perhaps reduce our genetic diversity, which might make us more vulnerable to some diseases. Another problem is that if we start making “designer babies”, it could worsen social inequalities — such a procedure is likely to be unaffordable for most people. Some people may also not consider it fair to make such decisions for a child, as it would affect their whole life, and it takes away their right to choose what is best for them.

In 2018, a Chinese scientist claimed to have created the first CRISPR-edited babies (edited a gene related to HIV resistance), which caused international outrage. The scientific community condemned the experiment, citing concerns about safety, ethics, and lack of informed consent (16). Interestingly enough, the success of editing or the “gene surgery” itself were not peer-reviewed or scientifically validated (16). It’s been six years since then, the attitude of the scientific community towards CRISPR-babies have not changed, and no other scientists have attempted to create genetically edited children.

CRISPR is an amazing scientific tool, but it’s important that people really understand what it can and can’t do. If the public gets the wrong idea, like thinking that CRISPR can easily create “designer babies”, it could lead to unrealistic hopes and unnecessary fear. This can lead to public backlash, pressuring governments to impose strict regulations that could slow down important research.

When the media sensationalizes CRISPR, it can create distrust, even when the technology is used for good purposes. This kind of misinformation can make people resist CRISPR, even when it could be used to treat serious genetic disorders or diseases like cancer. For the technology to advance in a safe and ethical way, the public must be informed in a just way.

Final words

So no, eugenics is not back. The babies are not engineered to have blond hair and blue eyes. The idea of “designer babies”, where CRISPR is used to customise human traits, sounds like something out of science fiction and can be scary. But the reality is much more complicated, and CRISPR isn’t as advanced as some headliners make it seem. It’s a powerful tool with amazing potential, but not quite capable of easily changing things like appearance.

The ethical concerns around using CRISPR for non-medical purposes are serious, and we need to be careful about what we do with the technology. Unfortunately, misleading information can create unnecessary fear and might even slow down important scientific progress.

In a world where “clickbaity” headlines and images often come before the truth, it’s difficult not to be misled. Be skeptical, ask questions, and keep searching for answers.

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References

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2. Tang, G., Qin, J., Dolnikowski, G. G., Russell, R. M., & Grusak, M. A. (2009). Golden Rice Is an Effective Source of Vitamin a. The American Journal of Clinical Nutrition, 89(6), 1776–1783. https://doi.org/10.3945/ajcn.2008.27119
3. McKie, R., & editor, R. M. S. (2024, May 25). “A catastrophe”: Greenpeace blocks planting of “lifesaving” Golden Rice. The Observer. https://www.theguardian.com/environment/article/2024/may/25/greenpeace-blocks-planting-of-lifesaving-golden-rice-philippines
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