On Editing the Genome

HMND
8 min readApr 20, 2023

Are you happy with your appearance? Surely you have features and secrets that make you feel insecure. Going on another date, do you think about how you will have a good time with a new potential partner, or are you preparing for it as a decisive battle, planning how you will hide your excess weight, mask skin defects, seem taller and slimmer, or on the contrary, specifically emphasise your advantages?

Or let’s imagine the parents of a child with a rare, disabling disease. While other children attend extra art classes or play football, their child is bedridden and completely deprived of the opportunity to satisfy his basic needs. Imagine yourself in the place of these parents.

And now they tell you that there is a new miracle cure that can solve your problem once and for all. How will you do it? Accept what nature has given you, or interfere with the natural course of things? Will it matter to you that society can condemn you? How much are you willing to pay for such deliverance, one or two years’ salary? What if you have to pay half your income for the rest of your life?

Our appearance is determined by our genetic material contained in DNA. Your eye color, body mass index, height, all this is written in our genes and inherited from our parents. We could not influence the set of our genes … until recently. Since the discovery of DNA and genetic information, people have not ceased to fantasise about editing it.

People can pursue completely different goals when editing the genome. The most common is the solution of medical problems. Nowadays, more than 6 thousand genetic diseases are known, many of them are not compatible with life, lead to disability, and none of them can be treated, we can only stop their symptoms. With the help of genome editing, you can defeat them all. It is possible that in a couple of hundred years these diseases will only be found in medical reference books, next to smallpox and polio (I really hope covid will also be there). Approximately 5–6% of the world’s population has genetic diseases, or genetic predispositions to diseases, moreover, each of us is a carrier of about 5 hereditary diseases that can kill or severely limit the quality of life of your offspring. That is why it is very difficult to overestimate the importance of gene therapy.

But this is only the tip of the iceberg; when editing the genome, the author of the project can pursue completely different goals, limited only by his imagination. You can make changes that will benefit the entire society, such as firefighters with fireproof skin, or a permanent gene vaccine against HIV for all newborns. And vice versa, for example, some dictator may want to create an army for himself from strong and fast, but devoid of will soldiers. Or a woman who has had dozens of plastic surgeries wants to give birth to a child with the features of her new appearance, no matter what the consequences. One can recall one of Stephen Hawking’s main fears, which is genetic modification of people from the upper class to the level of superhumans, and the rest of society will remain, at best, at the same level. A terrible dystopia, with the division of all mankind into slaves who must grow up quickly, fulfill their social role and die before old age and masters — forever young, strong, smart, endlessly amusing their ego. Society can follow a variety of paths of development, I am sure that some of them cannot be imagined by any science fiction writer now. But it is absolutely obvious that humanity itself will begin to create its own evolution, reducing the effect of natural factors to zero.

But regardless of the above, before you edit the genome, you need to decide on modern methods. Globally, all methods are either add or remove genetic material, here’s a roundup of the most promising and prolific methods.

Tissue nanotransfection (TNT)

One of the safest and most effective genome editing methods is nanochannel or nanoelectroporation. In this method, synthetic RNA and DNA are loaded into a special device with a microchip. Embedded in the chip are tiny needles containing nanochannels into which synthetic RNA and DNA are loaded. The biological cargo is delivered to the cells with the help of a small electric charge, which is practically not felt by the patient. This procedure takes less than a second and demonstrates 98% efficiency. Also, using this method, cells can be reprogrammed, that is, from cells of one type of tissue, cells of another type of tissue can be obtained. It can be very useful in the future, when it will be possible to grow a full-fledged organ, for example, a kidney, from a patient’s adipose tissue.

Viral vectors

The essence of the method is that the patient is infected with a virus with altered genetic material that is unable to reproduce. As a result, the patient receives the gene he needs, without the risk of transferring an infectious disease. Examples of the use of this technology are covid vaccines: BNT162b2 (BioNTech and Pfizer) or AZD1222 from AstraZeneca. I also want to mention the Zolgensma vector drug used to treat spinal muscular atrophy, which has a phenomenal cost of $ 2.1 million (the price is current for February 2023).

Removing unnecessary genes

CRISPR/Cas9, TALEN, and the zinc finger method are technologies that allow us to remove unwanted DNA from our genome. All of them work, approximately, according to the same scheme, these are particles that have in their composition a part responsible for recognizing a target in the genetic code and an enzyme responsible for cutting DNA.

For example, a person has an increased synthesis of the amyloid protein, leading to the development of various diseases, such as Alzheimer’s disease. We cut out the gene responsible for the synthesis of this protein, eliminating the root cause of the disease. Also, with the help of a combination with TNT, it is possible to cut out broken genes and insert normal ones. This method can be used to treat many autoimmune diseases, such as diabetes. One of the main problems of all genome editing methods is mosaicism. At the moment, it is not possible to introduce genome-editing agents into 100% of target cells; this leads to reprogramming of only a “partial” fraction of cells. Although it is worth noting that for the treatment of many diseases, for example, Duchenne myodystrophy, 1% of reprogrammed cells is enough.

Where are we now?

If it seems to us that editing the human genome is only possible in the far future, then it is worth remembering the loudest example of the use of technology on humans. In November 2018, it became known that a team of Chinese scientists led by He Jiankui managed to create the world’s first people with artificially modified genes (CCR5 is disabled) — two twin girls who are supposed to be immune to the human immunodeficiency virus. The experiment was criticized for violating numerous scientific and ethical rules. But the fact of creating genetically modified people will forever remain in the history of world science.

Against the backdrop of official science with its ethical committees and set of rules, the Odin project https://www.the-odin.com/ looks very interesting. The project staff position themselves as biohackers, making genome editing technology available to everyone. Odin’s team argues that everyone should be able to prepare reagents in their kitchen to edit those elements in their genome that do not suit them. Ideas have been repeatedly expressed to reduce the income of the beauty industry, pharmacology, and medicine due to the mass use of genome editing technology. CEO Josiah Zayner has already experimented with blocking myostatin using CRISPR / Cas9 technology and tested his own covid vaccine with friends. The company also sells laboratory equipment and reagents for the practice of self-editing the genome at home. Of course, you won’t be able to change your eye or hair color, but you will be able to feel like a real scientist and make the yeast glow in the dark, and then brew a glowing beer.

Among the potential side effects of genomic modification are carcinogenesis, the development of autoimmune diseases, disruption of the integrity or regulation of other genes in cells, as well as necrosis and anaphylactic shock. The human genome is still being studied and not all pathways have been studied, no one can guarantee that you turn off the gene responsible for gout and at the same time you will not have kidney stones, mental retardation and water retention in the body. These side effects, quite often, are delayed in time, and therefore are often not indicated in the short-term results of the study. Animal models also do not always answer the question of the safety of a particular operation, since the mechanisms of genetic regulation in all living organisms are different.

For widespread use in humans, it is necessary to verify the safety of the technology, the level of survival of transfected cells, find the best way to calculate the dosages of administered substances, and most importantly, learn how to modify all cells of the body/target organ/tissue, and not just a few percent.

Societal concerns

At the moment, there is no consensus in society about the benefits of genome editing. People evaluate this problem through the prism of their stereotypes, knowledge and religious beliefs. Let’s look at some charts from social surveys:

People with higher the religious beliefs are more likely to reject the idea of genetic editing
How can awareness of genomic editing methods influence the decision to use the technology? Everything is logical, uninformed people are more afraid of a procedure that they know little about and that is incomprehensible to them.

Few celebrities, such as Bill Gates and John Oliver, have championed the positive potential of CRISPR. However, the pioneer of human genome editing, He Jianguo, was punished with a three-year prison sentence and a fine of 3 million yuan.

In conclusion, it is worth saying that genetic modification is not a walk in a park, it is more like wandering in a labyrinth, surrounded by almost complete darkness. By correcting one defect, we can create a cascade of several new ones. Genome editing must be carefully studied, new pathways must be found, and more experiments should be carried out.

Ethical issues also need to be addressed as technology advances. What is acceptable today was unacceptable 100 years ago and was punishable 1000 years ago. Perhaps future generations will be faced with a moral choice that we never dreamed of. And most importantly, which way will we go when editing the genome? Humanity has repeatedly been on the verge of extinction due to natural disasters, and who knows if the ideal genetically modified people of the future will be able to withstand the repercussions of the explosion of the Yellowstone super volcano, or climate change, all thanks to having a set of modified genes?

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