"Editing Humanity" by Kevin Davies (College Assignment Book Summary)

“Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing” by Kevin Davies (published in April 2020)

I wrote the below essay/summary/review for an assignment for a genetics college course I took in 2021. I figured I may as well give the assignment some new life rather than not be read by anyone ever except the professor of the class.

I recall I had some choice in selecting a broad option of books related to genetics. I selected this one because I've always found gene-editing interesting and so it felt like reading the book would be an engaging read.

The most interesting part to me about the below essay is the discussion about the scientist who performed gene editing on babies, and why it was considered by many to be an unethical experiment. I feel that I nicely summarized the arguments and presented them logically to show why it is framed as unethical. The last paragraph teases some interesting discussion about the potential impacts of gene editing on society, which is worth discussion elsewhere perhaps, but it's not the focus on the essay.

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Review of “Editing Humanity: The CRISPR Revolution and

the New Era of Genome Editing” by Kevin Davies

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In “Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing”, Kevin Davies crafts a compelling story of how CRISPR technology was developed, the different characters behind advancements and controversies in the field, and how a world with CRISPR might look. The book is divided into four parts, each covering a different aspect of CRISPR and its impact on science and society.

In the first section of the book, Davies explores the researchers and experiments that led to the discovery of CRISPR. He makes an emphasis that the discovery of CRISPR shows the importance of performing basic science that isn’t necessarily “fashionable”: CRISPR was discovered during analysis of gene sequences of bacteria for research purposes completely unrelated to gene editing.

The second section of the book begins with a discussion of several genome editing and gene therapy technologies that existed before CRISPR. Davies then discusses several medical applications that CRISPR could impact, describing the clinical trials that are currently underway for diseases such as cancer and sickle cell disease.

In the third section, Davies covers a major event that recently took place in the field of CRISPR and genome editing: a Chinese scientist, He Jiankui, conducted research where human embryos underwent germline editing via CRISPR. Davies discusses He’s academic background, his experiments, and the backlash from the scientific community when the research came into the public light.

In the fourth section, Davies delves into other potential applications of CRISPR, such as de-extincting species, sterilizing disease-carrying mosquitoes, and increasing yields in agriculture. The section also describes advancements in CRISPR technology, such as the ability to make a single base replacement with higher accuracy and less off-target effects. Finally, Davies covers different ethical perspectives related to the use of germline editing to provide enhanced human traits to offspring, such as enhanced intelligence or perfect musical pitch.

Taking up an entire six-chapter section of the book, the discussion of He Jiankui’s act of germline modification in 2018, leading to the birth of three gene-edited babies, is a major topic in any discussion on the ethics of genome editing. This scientist’s research came as a shock to the scientific community and became a news sensation as the births of the “CRISPR babies” were revealed. He’s research violated ethical standards of science and his decisions have the potential to have a harmful impact on both the gene-edited babies and the scientific community.

He’s experiment sounds promising and justified at the surface level: to provide babies with immunity to HIV infection by inactivating the gene that allows infection to occur. However, there are several key points that bring He’s efforts into ethical question. First is that performing gene editing on an embryo went against the scientific consensus at the time, because the safety and effects of such a procedure had not yet been extensively studied. Some may view He’s research as one such study of CRISPR’s safety, but there likely are more incremental steps in studying the safety further without going so far as potentially harming a human being.

Secondly, a large reason why many frown on He’s research is because it did not address an unmet medical need, and so the modifications made were in a sense unnecessary. There are currently medical interventions that allow a person infected with HIV to lead a normal life and not be able to transmit HIV. Additionally, a man with HIV who does not want to pass it on to his offspring can undergo a procedure such as sperm washing to ensure HIV is not transmitted to his offspring. Taking the risk, however small, of some unknown effect of gene-editing was simply not worth it in this case, because the modification was simply not needed.

Thirdly, scientists’ concerns with He’s research were amplified even further when the study’s research paper revealed the slipshod nature of the edits that were made to the embryos’ genomes. The mutation that is known to provide immunity to HIV, called the “delta 32” mutation, consists of the deletion of 32 base pairs in the CCR5 gene. However, none of the edits that He’s team performed matched the delta 32 mutation. Instead, as revealed by the sequenced genomes, the edits included various lengths of insertions and deletions to the genes, with different edits across each embryo. For instance, one of the genes contained a 15 base pair deletion rather than the known 32 base pair deletion. Another embryo contained a 4 base pair deletion in addition to a single base pair insertion. These modifications were made with the hope that the changes would disrupt the gene’s function and thereby prevent HIV infection. However, these edits to the human genome have never been seen or tested before, so it is not certain whether those specific edits would actually lead to HIV immunity or whether there would be any unknown effects of the modification. Furthermore, the delta 32 mutation is known to be effective against HIV only if it is homozygous (mutated on both chromosomes). However, one of the babies was made to be heterozygous for the edits, providing even more uncertainty as to whether the edit would actually confer immunity to HIV.

The impacts of the modifications on the “CRISPR babies” may not be known for many years. The gene edits may confer immunity to HIV, they may lead to negative side effects, or they may not have any effect at all. The possibility of negative effects, especially when the intervention was not medically necessary, highlights the unethical nature of the act. Additionally, the slipshod nature of the experiments, creating novel and untested sequences in the CCR5 gene, shows a carelessness for the lives of the children and the potential consequences that may arise. Additionally, the children may be subjected to tests and research until they are 18 years old, which could be a physically or emotionally uncomfortable experience. Another effect that isn’t often discussed is that there may be undesired public scrutiny on the three children if their identities become publicly known.

The scientific community and those who could be benefited by future germline editing are also stakeholders when considering the ethics of the research. The publicity from He’s experiments could lead to mistrust in CRISPR technology and gene editing. In particular, if the edited babies end up experiencing negative effects as a result of the modification, this could be a major blow to further research in germline editing, potentially pushing back research and advancements for years. A consequence of this would be the deprivation of those who would benefit from germline editing, such as couples who have a homozygous dominant disorder that they don’t want to pass to their offspring. For such a case, germline editing would be the only option to prevent the disorder from being inherited. Without germline editing, if the couple chooses to still have a child, the baby would be born with a potentially debilitating disorder. It perhaps is overly dramatic to say that He Jiankui’s actions would be the cause of situations like this, but delays in research undoubtedly could negatively impact people by delaying the availability of clinical gene-editing procedures.

This discussion brings up the broader question of under what circumstances germline editing should be allowed, if ever. Beyond occasions where germline editing is the only option to prevent a known genetic defect in an offspring, many scientists believe that germline editing should only be used as a last resort. One reason for this hesitancy is because of the complexities of the human genetic system, making it difficult to predict the full impact of even one slight modification. Furthermore, many people fear the societal effects that could arise if genetic alterations to more superficial traits such as appearance and intelligence levels are allowed. However, much more about the human genome must be learned before modifications like these could become possible, if at all. Gene editing technology will need to undergo significant advancements before an experiment like He Jiankui’s can be ethically repeated, and in particular the safety of germline modifications will need to be studied in depth before such interventions can proceed.