Introduction

This article provides some reflections on questions around gene editing technologies. For this, I discuss genetic modification, which involves any process where genes are modified, either randomly by chemicals or by radiation, with specific attention to gene editing. The focus is predominantly on the gene editing technology ongoing in the medical community and the gene editing we could see in the future, including whether we should do it and if there should be limitations to its use. I consider gene editing or genetic engineering to be any technology that allows for the modification of genetic material from its natural form.

Should we do genetic modification? We already do. Among the first applications of genetic modification was the development of genetically modified crops, first produced in the 1920s using radiation and chemicals to cause genetic modification and then selecting those plants that had the desired traits (often resistance to a particular infection). As technology developed, relatively crude approaches could be used to create specific modifications rather than random generation with the selection of traits one desired. Similarly, agricultural methods for beef and pork found that conventional breeding choices already produced the meatiest animals possible and further modification was not useful. Attempts to use genetic engineering to enhance the results for beef and pork production were not beneficial compared to the conventional technology.

Should we do genetic engineering? We already do this as well (National Academies of Science, Engineering, and Medicine 2017). Technologies that came about from the use of proteins called restriction enzymes isolated from bacteria allowed for the cutting of DNA at distinct locations; what was random in the past could now be designed. For example, recently, genetic engineering approaches have been used to develop plants and crops that are resistant to certain physical stresses, such as droughts or heat, and designed to survive hostile environments. This allows for crop production in circumstances where food may be limited. As a result, gene editing (used to produced genetically modified crops) may help feed populations that might not otherwise might be able to raise sufficient food. While this has been considered somewhat controversial in some areas of the world, genetically modified crops have been in use for decades and have solved some world hunger problems (Center for Food Safety and Applied Nutrition 2023).

While conventional breeding had already produced cattle and bovine that were ideal for consumption, this was not the case with fish, where breeding efforts have not been as extensive. When genetic engineering approaches provided fish genomes with additional growth hormone genes and other genes that improved growth, bigger and meatier fish were possible. In fact, some North American states (Minnesota, for example) sought to improve fishing tourism by stocking lakes with very large fish genetically engineered.

Somatic vs Germ Cell Engineering

Somatic cells are those cells that make up the body, and germ or germ line cells are eggs and sperm that lead to offspring. Much has been done in both somatic and germ cells of nonhuman species using techniques that are error-prone and inefficient. In some examples, lab animals have been used to examine research questions about how genes are turned on and off in tissues, how particular genes function in disease and normal situations, what gene changes affect function, and more (Hall et al. 2009). Often, gene editing is used as a tool to produce certain proteins needed for human treatments. For example, in the past, humans with diabetes were given insulin derived from pigs and other animals; eventually, some of the people who received these treatments became resistant to the insulin and it could no longer be used. There was a need to generate human insulin in large quantities, and so gene editing was used. Germ line DNA of cows (from cow eggs) was modified to contain human insulin driven by a piece of DNA that allows for production of the protein in cows’ milk. When the cows are milked, the milk contains large quantities of insulin and can be purified for use in humans (Khodarovich et al. 2013). This allows humans to have human insulin to help treat diabetes. This technique is used to produce countless other proteins in many other organisms, from bacteria to mammals. When proteins are labeled as being “recombinant,” they were usually produced using this type of gene-editing approach (Woloschak 2014).

The first genetically modified mammals were mice developed in a laboratory in 1974 (National Research Council 1994) in an effort to understand how genes are regulated (i.e., how they are turned on and off in particular cells). These were genetically engineered to contain a DNA sequence in particular tissues that made the animal glow in the dark. The work helped scientists understand how and when in development particular genes are expressed. This was revolutionary for its day. It is now considered a routine approach used in labs to examine the effects of various types of genetic changes on function and to understand how different genes with different characteristics are regulated. Like much technology, this method has developed from being difficult and complex to achieve to being a routine and mundane procedure. Initially, the work could be done in only a few labs in the world; now, it is routinely done in most molecular biology laboratories.

Gene Editing in Humans

Should we do gene editing in humans? We already do this too. All techniques currently approved for use in humans involve the use of somatic cells, i.e., those cells that make up the body, not the germ line cells that would be passed on to offspring. To date, most gene editing in humans has been used to treat single gene deficiency diseases, which are usually in a single cell type that can be modified. This actually represents a very small number of human diseases that have a genetic component. Most complicated diseases like coronary heart disease, cognitive disorders, or diabetes have multigenic causes; therefore, approaches to gene editing to repair those abnormalities require information and technology not currently known. In addition, most gene editing approaches have used gene replacement and not modification of an existing gene (more on this later). The concept behind this approach is that if a gene is defective, the way to remedy it is to just put in the correct gene, not to try to edit the defective gene already in existence. Technology to edit the existing gene has been limited and difficult and was done employing older technologies of gene editing before the development of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and other methods (discussed later).

So why would one want to pursue the development of a genetically modified human being? There are genetic diseases that can be cured by the transfer of a single gene. These are genetic disorders where only one gene is dysfunctional, and thus replacement of that one gene allows for the complete correction of the problem in the person. An example would be children who have been born without an immune system and are placed inside bubbles to keep them from catching infections they cannot fight and that will be fatal for them. These children have been treated with a single gene engineered into a virus that contains the correct gene, and that gene lives alongside the altered mutated gene sitting in the child’s genome. This common approach toward gene editing has some risks, but often it is used to treat a disease that is nearly fatal; therefore, the benefits outweigh the risks. These and other somatic cell modifications have been successfully attempted for a variety of different conditions, including cancer, hemophilia, certain types of blindness, and others. There are only a few genetic diseases caused by a single gene in a single cell type that can be addressed using this technology. New approaches are needed for multigenic diseases (such as diabetes) and diseases that affect multiple different types of cells in the body (Duchenne muscular dystrophy, for example).

Based on the fact that most genetic diseases fit into these categories of being either multigenic or affecting multiple cell types in the body, a significant question for humans is: Should we do gene editing in germ line cells (the eggs and sperm) so that all the cells of a person would be corrected for the problem? Until now, gene editing has not been used in human germ line cells due to concerns about the introduction of a genetic change into a person that could be passed from generation to generation and live in the human population forever. In addition, earlier technologies before CRISPR had limitations.

Prior to the development of genetic engineering, physicians employed the broad field of genetic testing and genetic counseling. This approach was initially used to confirm a suspected diagnosis of a disease, to predict the possibility of future illness, and for prenatal diagnosis. With the expansion of uses of genetics beyond testing and into therapy, genetic counseling has become even more critical. Degrees in genetic counseling are now offered by many universities in an effort to provide a workforce that is educated in the techniques and information of molecular genetics. These counsellors are trained to explain the complicated nature of genetic disease, provide approaches to mediate and facilitate treatment among family members, and to help people prepare for future decisions. In addition to professional genetic counseling, pastoral counseling may be of great benefit to the patient and the family; one would anticipate that pastoral counseling would provide an opportunity for the patient to express concerns, but also help them cope with results, particularly if they are difficult, and aid in discussion about long-term consequences. Improved communication and collaboration among pastors and health professionals could facilitate this work. This becomes especially important as the number technologies increases the decision points in people’s lives.

Human Gene Pool

Also important to this discussion is the human gene pool. A gene pool refers to the combination of all the genes present in a reproducing population of a species. The human gene pool contains all the genes that could ever exist in the entire human population that are capable of reproducing. A large gene pool has extensive genetic diversity and is better able to withstand environmental changes than a small gene pool. For example, in tiger species where there is little diversity among them, one or two infections can wipe out a large number of the population. A large gene pool is important to enhance the survival of a species, particularly when faced with environmental challenges. It should be remembered that the gene pool refers to those genes in reproductive or germ line cells and not in somatic cells; thus, when modifications are made to somatic cells, those changes will not be passed onto the offspring, but when modifications are made to germ line cells, they will be passed on to the offspring for generations in the future.

The makeup of a population’s gene pool can change naturally overtime through the process of evolution. This can occur by a variety of mechanisms, including natural selection, mutations, and genetic drift. The result is a gene pool that is altered to be attuned to the needs of the population’s particular environment. Humanity’s past gene pool contributes to the gene pool of today, and today contributes to tomorrows. Changes in the gene pool made in the past will be reflected in today’s gene pool, changes in germ line gene frequencies will change the gene pool, perhaps in small ways at first, but possibly in larger ways in the future. At the moment, it is impossible to predict the impact of how interfering with humanity’s gene pool will affect humanity in future generations. In general, alterations in a somatic cell genome will cause changes to that individual but will not be passed on to the offspring, and thus pose no danger to the integrity of the gene pool.

One concern with genetic manipulation of human eggs and sperm is the hubris that claims scientists can predict the impact of modification of the human gene pool for even one gene much less the many genes that would be required for gene editing of the more common multigenic diseases. Only very small components of gene function are known, and this knowledge of course changes over time as more is learned about a particular disease and a particular gene. Only for the simplest of genetic situations do we understand the impact of gene changes in somatic cells. In addition, many genes have multiple functions, and even if we know one, we may not know them all.

The example of sickle cell anemia/thalassemia demonstrates how little was understood even a few years ago. People with two mutant copies of the sickle cell hemoglobin gene die of sickle cell anemia/thalassemia. People with two normal copies living in Africa or the Mediterranean, where malaria is endemic, are very susceptible to malaria and often die of it. But in regions where malaria is endemic, people with one normal copy and one mutant copy can survive malaria and do not die of sickle cell anemia thalassemia either; there is a strong relationship here between environment and ecology that makes malaria a selection factor for one copy of the sickle cell gene. Without the sickle cell gene, humans would not have survived malaria and could not have made it “out of Africa” (de Lange 2011). Nevertheless, sickle cell anemia in North America today is thought of only as a “bad gene” to be removed from the human population. We do not appreciate its role in helping fight malaria in Mediterranean and African populations. This is an example of a “bad” gene that serves an important function in the human gene pool. Its elimination could have significant consequences for humanity.

There are other examples of “bad genes” with “good functions.” When mutated, the BRCA1 gene is associated with the development of breast cancer, which is how it was named. Nevertheless, there are some data that support the idea that women with one copy of the mutated (“bad”) BRCA1 gene and one copy of the “good” gene have increased fertility (Kwiatkowski et al. 2015). Genes associated with Alzheimer’s, which is a very complex disease, may have protection against kidney damage. Angiotensin converting enzyme genes are associated with living to an old age but also with heart disease and, more recently, poor survival from COVID-19.

The context here is that genes can be good or bad depending on the tissue, the time when they are active, the presence or absence of other genes, the sex, the life history of the person, and much, much more. For multigenic traits, even such things as a virus infection at a particular age or exposure to an environmental toxin can influence whether disease results or not; most disease is not simply genetic. It is a combination of genetics and environment. In addition, some health issues we call disease may really be variations of normal, as exemplified by the sickle cell trait, which actually allows for improved survival from malaria.

For humanity, there is a strong desire to eliminate suffering, and this too is something that must be considered here. We can imagine eliminating diseases like Duchenne’s muscular dystrophy, which leads to severe muscle breakdown by a young age (see, e.g., Chen et al. 2022); Parkinson’s Disease, which leads to neurological breakdown (see, e.g., Rahman et al. 2022); Tay-Sachs disease, which leads to death by three to five years of age; or Huntington’s disease, which leads to death between the ages of ten and twenty-five years. Some of these are single-gene disorders and could be corrected using straightforward approaches; the problem is that they must be corrected at the level of the embryo since multiple different cell types in the body become affected by the disorder. Muscular dystrophy cannot be corrected only in somatic cells because there are so many somatic cells affected by this single gene that not all could be corrected to prevent the disease development. In other examples, multiple genes are involved, and correction of all of them in the germ line would be required to prevent the genetic problem (Sivakumaran et al. 2011).

Treatment of serious neurocognitive disorders can also be considered in this therapeutic approach, but here even more complicated situations might arise. The genes associated with neurocognition may also be important in personality development. It is possible that in modifying the many genes associated with schizophrenia, for example, may produce results that affect the personality development of the individual; determining whether this has occurred would be very difficult to monitor since personality is not easily subjected to examination.

If we have the ability to cure these diseases and do not use our energy to do so, what can we think about ourselves? Alternatively, some suffering is unavoidable. It needs to be accepted and even embraced.¹ How do we work through the balance of when to treat and when not to treat? An overarching consideration for all of these questions is economics; in some examples, treating or even curing a long-term disease may be less expensive than providing medical care through the duration of an illness for a debilitated patient. Yet, it is also likely that gene editing technologies will be expensive and available to only a few, thus enhancing the distance between the “haves” and the “have nots.”

Ethics of Human Experimentation

In the 1940s, concerns arose about the dangers of human experimentation. Many countries had performed experiments on populations without their permission. The United States is noted for exposing African American populations to syphilis, not telling them about it, reporting their symptoms, and never treating the disease. The Nazi regime conducted large numbers of experiments on human prisoners and underrepresented populations, including parachute testing, drug testing, studies to determine how different ethnic groups withstand infections, and more, all done without the consent of the population studied. When these atrocities came to light, medical populations collectively considered approaches to safeguard and protect people from such unapproved experimentation. As a result, panels to examine the ethics of human studies were developed in most major countries of the world (Woloschak 2020).

At this point in history, ethical concerns for human subject considerations are governed by institutional review boards (IRBs) that safeguard the patient and protect him or her from harm. In the United States, no experiments can be done with humans (from simple surveys to the administration of drugs to genetic modification) without first going through a series of complicated approvals and meetings to ensure the safety of the human subject is protected. This has also been developed strongly in Canada and most western European nations; approaches similar to IRBs are used wherever human studies are performed. Most IRBs in the United States are managed by hospitals, which have committees including members of the general public, clinicians, researchers, lawyers, and others all trying to discern whether a particular treatment is in the patient’s best interest and whether it will contribute to scientific or medical understanding as designed. No human study can be initiated until an IRB has been approved for the work.

As noted, the purpose of an IRB is to protect individual human subjects, but who is responsible for protecting the human population and the human gene pool? IRBs do not consider anything except the individual patient. How do we balance saving individual lives and suffering with a potential risk to the human gene pool? When can we be certain the risk is low? It is clear more reflection on potential damage to the human gene pool and the human population at large is needed prior to even considering genetic manipulation of germ line cells, which will affect the human gene pool forever. Finally, most studies of effectiveness of a particular therapy involve studies of at most ten or twenty years. For gene pool studies, studies would need to be initiatd examine humans through multiple generations, an approach the scientific community has rarely attempted.

Which Genes to Edit?

A further question that has become important when considering editing the human genome at the level of eggs and sperm is the fact that some genetic engineering could be done for frivolous reasons. There are already examples of the selection of babies for IVF that have particular traits such as blue eyes and blonde hair; originally, this approach was used in order to select against offspring that might have or carry a particular unwanted genetic trait. Later, this technology was exploited to include designer babies that could have features the parents wanted. This is done in vitro so that only those embryos with the selected genes are implanted into the womb of the expected mother; generally, the selection has been made based on whether particular desirable proteins are present in the embryo.

In this example, the technology previously used to prevent disease was further expanded upon (usually for a large fee) to select for babies that have desired features (rather than undesired diseases). In the same way IVF technology has been exploited, so is it possible to turn around gene editing technologies. First, they will be developed to prevent certain diseases, but later, the approach can be expanded to include other, less damaging but perhaps also undesirable, traits. What might start out as a treatment for muscular dystrophy or Tay Sachs disease could later turn into eliminating left-handedness or introversion, for example. Are these appropriate uses for gene editing technology? If one considers that there may be some risks associated with it (for example, affecting the human gene pool), then taking the risks to eliminate disease might be a much greater priority than using the technology to select for babies that are, for example, right-handed or are very tall. It should also be noted that this technology is very expensive, at least at this juncture, and it is likely that more opportunities for genetic engineering would be available to those who can afford it rather than the broad population.

With the elimination of disease becoming a goal of gene editing technology, neurocognitive disorders and psychological diseases are likely to become a major target for attempted therapies. These disorders are debilitating and heartbreaking for those involved. Schizophrenia, for example, is a disabling psychological disorder that is associated with at least 108 different genes (Trifu et al. 2020). Like schizophrenia, most neurocognitive disorders in general are complicated and involve the interaction of many genes, in some cases with environmental factors. Efforts made to identify their underlying pathology have been confusing and complicated. In my opinion, this type of tampering brings science dangerously close to altering the human personality if not the human person, since many of these genes appear to play roles in personality development. One could imagine how tampering with the schizophrenia-related genes in an effort to eliminate psychological diseases might have a dubious effect on the human population, since most of these genes are multifunctional and have broad-ranging impacts. How would humanity know where to stop once this has begun, since effects on the human population as a whole may not be realized for several generations?

Concluding Thoughts

Applications of gene therapy from the genome of somatic cells into germ cells come with a new set of considerations that have implications for the future of humanity. Changes made in germ line cells can lead to irreversible changes in the human gene pool with implications for the future of humanity. Current methods of ethical review do not examine long-term effects and scientific approaches for the consideration of future consequences. These changes cannot be tested in a research system that tests for years instead of generations.

There are also concerns about how genes would be selected for germ line editing. For diseases that have a one-gene cause, this could be determined in a straightforward way. For multigenic diseases like diabetes or coronary artery disease, the genetic modifications could be quite complicated and could have effects other than those predicted by the modification itself. These effects might limit the use of the technology for germ line cells. Pushing this issue even further, the treatment of neurocognitive conditions could lead to even more complicated problems, such as changes in genes that affect personality and awareness.

For both reasons, the potential risks associated with this work may be significant, and a renewed discussion on the ethics is required from alternate perspectives to gain insights into approaches for the future. Decisions about moving technology require wisdom, not just “knowledge,” and discernment, not only “awareness.”

Some of this dialogue is ongoing in the Christian community already, with commentaries on both sides of the gene editing debate. What can the Orthodox offer to this dialogue? The Orthodox have a unique understanding of personhood and what it means to be a human person. Reflections on gene editing in light of the human person would be important, especially considering the possibilities of it affecting psyche and personality. Orthodox are also capable of having a balanced view toward science that examines it not only as a tool to be used for human purposes but also as a gift from God and a means of asking questions that challenge humanity. For Orthodox, it is not always about getting to an answer but also how the journey is made to get to that point. For gene editing, answers alone are important but perhaps not sufficient for a deep understanding; how we get to those answers will help to drive questions in the future.

As Metropolitan Anthony Bloom has written: “Our task is not merely to imitate what was done by the saints of previous eras, but somehow to appropriate at a much deeper level the way in which they engage their own historical environment, seeking to respond as they would have responded had they lived in our day.”

Acknowledgments

The author wishes to thank Rev. Lori Shinko Snyder for her help in preparing this manuscript for publication.