Is Genetic Engineering And Modification Our Future?

I have written several articles on the coronavirus and on masks and healthcare issues. A series of links have been provided at the bottom of this article for your convenience. This article will, however address a different aspect of the virus or on healthcare issues in general.

Genetic modification is a technique to change the characteristics of a plant, animal or micro-organism by transferring a piece of DNA from one organism to a different organism. This is done through targeted removal of the desired genes from the DNA of one organism and adding them to the other organism.

Genetic engineering is the process of using recombinant DNA (rDNA) technology to alter the genetic makeup of an organism. … Genetic engineering involves the direct manipulation of one or more genes. Most often, a gene from another species is added to an organism’s genome to give it a desired phenotype.

What is genetic engineering?

  • Genetic engineering, sometimes called genetic modification, is the process of altering the DNA? in an organism’s genome?.
  • This may mean changing one base pair? (A-T or C-G), deleting a whole region of DNA, or introducing an additional copy of a gene?.
  • It may also mean extracting DNA from another organism’s genome and combining it with the DNA of that individual.
  • Genetic engineering is used by scientists to enhance or modify the characteristics of an individual organism.
  • Genetic engineering can be applied to any organism, from a virus? to a sheep.
  •  For example, genetic engineering can be used to produce plants that have a higher nutritional value or can tolerate exposure to herbicides.

How does genetic engineering work?

To help explain the process of genetic engineering we have taken the example of insulin, a protein? that helps regulate the sugar levels in our blood.

  • Normally insulin? is produced in the pancreas?, but in people with type 1 diabetes? there is a problem with insulin production.
  • People with diabetes therefore have to inject insulin to control their blood sugar levels. 
  • Genetic engineering has been used to produce a type of insulin, very similar to our own, from yeast and bacteria? like E. coli?
  • This genetically modified insulin, ‘Humulin’ was licensed for human use in 1982. 

The genetic engineering process

  1. A small piece of circular DNA called a plasmid? is extracted from the bacteria or yeast cell.
  2. A small section is then cut out of the circular plasmid by restriction enzymes, ‘molecular scissors’.
  3. The gene for human insulin is inserted into the gap in the plasmid. This plasmid is now genetically modified.
  4. The genetically modified plasmid is introduced into a new bacteria or yeast cell.
  5. This cell then divides rapidly and starts making insulin.
  6. To create large amounts of the cells, the genetically modified bacteria or yeast are grown in large fermentation vessels that contain all the nutrients they need. The more the cells divide, the more insulin is produced.
  7. When fermentation is complete, the mixture is filtered to release the insulin.
  8. The insulin is then purified and packaged into bottles and insulin pens for distribution to patients with diabetes.

Illustration showing how genetic modification is used to produce insulin in bacteria.

An illustration showing how genetic modification is used to produce insulin in bacteria.
Image credit: Genome Research Limited

What else is genetic engineering used for?

  • The first genetically modified organism to be created was a bacterium, in 1973.
  • In 1974, the same techniques were applied to mice.
  • In 1994 the first genetically modified foods were made available.
  • Genetic engineering has a number of useful applications, including scientific research, agriculture and technology.
  • In plants, genetic engineering has been applied to improve the resilience, nutritional value and growth rate of crops such as potatoes, tomatoes and rice.
  • In animals it has been used to develop sheep that produce a therapeutic protein in their milk that can be used to treat cystic fibrosis, or worms that glow in the dark to allow scientists to learn more about diseases such as Alzheimer’s?.

Alzheimer’s disease and the worm

  • The nematode worm, C. elegans, only has around 300 cells in its entire nervous system, making it a very simple model for studying Alzheimer’s disease.
  • Also, due to the fact the worm is nearly transparent, when their nerve cells are labelled with green fluorescent protein (GFP), it is possible to watch the location and activity of various structures and proteins under the microscope.
  • The genetic material of C. elegans can easily be genetically modified to make the worm produce specific proteins the researchers want to study.
  • In humans, the APP gene codes for a protein associated with the amyloid plaques that are characteristic of people with Alzheimer’s disease.
  • So, to study Alzheimer’s, the researchers genetically engineered the nerve cells of the worm to contain the APP gene, effectively giving it Alzheimer’s.
  • By tagging the APP protein produced in the worm with green fluorescent protein it was possible to see that all the cells that made contact with APP died as the worm got older.
  • The researchers were then able to monitor the progression of Alzheimer’s disease in the worm and go on to apply their findings to understanding the role of APP in humans with Alzheimer’s disease.  

Human enhancement: Genetic engineering and evolution

INTRODUCTION

There are countless examples where technology has contributed to ameliorate the lives of people by improving their inherent or acquired capabilities. For example, over time, there have been biomedical interventions attempting to restore functions that are deficient, such as vision, hearing or mobility. If we consider human vision, substantial advances started from the time spectacles were developed (possibly in the 13th century), continuing in the last few years, with researchers implanting artificial retinas to give blind patients partial sight. Recently, scientists have also successfully linked the brain of a paralysed man to a computer chip, which helped restore partial movement of limbs previously non-responsive. In addition, synthetic blood substitutes have been created, which could be used in human patients in the future.

The progress being made by technology in a restorative and therapeutic context could in theory be applied in other contexts to treat non-pathological conditions. Many of the technologies and pharmaceutical products developed in a medical context to treat patients are already being used by humans to ‘enhance’ some aspect of their bodies, for example drugs to boost brain power, nutritional supplements, brain stimulating technologies to control mood or growth hormones for children of short stature. Assistive technology for disabled people, reproductive medicine and pharmacology, beside their therapeutic and restorative use, have a greater potential for human ‘enhancement’ than currently thought. There are also dual outcomes as some therapies can have effects that amount to an enhancement as for example, the artificial legs used by the South African sprinter Oscar Pistorius providing him with a competitive advantage.

This commentary will provide general ethical considerations on human enhancement, and within the several forms of so-called human biomedical enhancement, it will focus on genetic engineering, particularly on germline (heritable) genetic interventions and on the insights evolutionary biology can provide in rationalizing its likely impact. These insights are a subject often limited in discussions on genetic engineering and human enhancement in general, and its links to ethical, philosophical and policy discussions, in particular. The rapid advances in genetic technology make this debate very topical. Moreover, genes are thought to play a very substantial role in biological evolution and development of the human species, thus making this a topic requiring due consideration. With this commentary, we explore how concepts based in evolutionary biology could contribute to better assess the implications of human germline modifications, assuming they were widely employed. We conclude our brief analysis by summarizing key issues requiring resolution and potential approaches to progress them. Overall, the aim is to contribute to the debate on human genetic enhancement by looking not only at the future, as it is so often done, but also at our evolutionary past.

HUMAN ENHANCEMENT

The noun ‘enhancement’ comes from the verb ‘enhance’, meaning ‘to increase or improve’. The verb enhance can be traced back to the vulgar Latin inaltiare and late Latin inaltare (‘raise, exalt’), from ‘altare’ (‘make high’) and altus (‘high’), literally ‘grown tall’. For centuries human enhancement has populated our imagination outlined by stories ranging from the myths of supernormal strengths and eternal life to the superpowers illustrated by the 20th century comic books superheroes. The desire of overcoming normal human capacities and the transformation to an almost ‘perfect’ form has been part of the history of civilization, extending from arts and religion to philosophy. The goal of improving the human condition and health has always been a driver for innovation and biomedical developments.

In the broadest sense, the process of human enhancement can be considered as an improvement of the ‘limitations’ of a ‘natural version’ of the human species with respect to a specific reference in time, and to different environments, which can vary depending on factors such as, for example, climate change. The limitations of the human condition can be physical and/or mental/cognitive (e.g. vision, strength or memory). This poses relevant questions of what a real or perceived human limitation is in the environment and times in which we are living and how it can be shifted over time considering social norms and cultural values of modern societies. Besides, the impact that overcoming these limitations will have on us humans, and the environment, should also be considered. For example, if we boost the immune system of specific people, this may contribute to the development/evolution of more resistant viruses and bacteria or/and lead to new viruses and bacteria to emerge. In environmental terms, enhancing the longevity of humans could contribute to a massive increase in global population, creating additional pressures on ecosystems already under human pressure.

Two decades ago, the practices of human enhancement have been described as ‘biomedical interventions that are used to improve human form or functioning beyond what is necessary to restore or sustain health’. The range of these practices has now increased with technological development, and they are ‘any kind of genetic, biomedical, or pharmaceutical intervention aimed at improving human dispositions, capacities, or well-being, even if there is no pathology to be treated’. Practices of human enhancement could be visualized as upgrading a ‘system’, where interventions take place for a better performance of the original system. This is far from being a hypothetical situation. The rapid progress within the fields of nanotechnology, biotechnology, information technology and cognitive science has brought back discussions about the evolutionary trajectory of the human species by the promise of new applications which could provide abilities beyond current ones. If such a possibility was consciously embraced and actively pursued, technology could be expected to have a revolutionary interference with human life, not just helping humans in achieving general health and capabilities commensurate with our current ones but helping to overcome human limitations far beyond of what is currently possible for human beings. The emergence of new technologies has provided a broader range of potential human interventions and the possibility of transitioning from external changes to our bodies (e.g. external prosthesis) to internal ones, especially when considering genetic manipulation, whose changes can be permanent and transmissible.

The advocates of a far-reaching human enhancement have been referred to as ‘transhumanists’. In their vision, so far, humans have largely worked to control and shape their exterior environments (niche construction) but with new technologies (e.g. biotechnology, information technology and nanotechnology) they will soon be able to control and fundamentally change their own bodies. Supporters of these technologies agree with the possibility of a more radical interference in human life by using technology to overcome human limitations, that could allow us to live longer, healthier and even happier lives. On the other side, and against this position, are the so-called ‘bioconservatives’, arguing for the conservation and protection of some kind of ‘human essence’, with the argument that it exists something intrinsically valuable in human life that should be preserved.

There is an ongoing debate between transhumanists and bioconservatives on the ethical issues regarding the use of technologies in humans. The focus of this commentary is not centered on this debate, particularly because the discussion of these extreme, divergent positions is already very prominent in the public debate. In fact, it is interesting to notice that the ‘moderate’ discourses around this topic are much less known. In a more moderate view, perhaps one of the crucial questions to consider, independently of the moral views on human enhancement, is whether human enhancement (especially if considering germline heritable genetic interventions) is a necessary development, and represents an appropriate use of time, funding and resources compared to other pressing societal issues. It is crucial to build space for these more moderate, and perhaps less polarized voices, allowing the consideration of other positions and visions beyond those being more strongly projected so far.

Ethical and societal discussions on what constitutes human enhancement will be fundamental to support the development of policy frameworks and regulations on new technological developments. When considering the ethical implications of human enhancement that technology will be available to offer now and in the future, it could be useful to group the different kinds of human enhancements in the phenotypic and genetic categories: (i) strictly phenotypic intervention (e.g. ranging from infrared vision spectacles to exoskeletons and bionic limbs); (ii) somatic, non-heritable genetic intervention (e.g. editing of muscle cells for stronger muscles) and (iii) germline, heritable genetic intervention (e.g. editing of the C–C chemokine receptor type 5 (CCR5) gene in the Chinese baby twins, discussed later on). These categories of enhancement raise different considerations and concerns and currently present different levels of acceptance by our society. The degree of ethical, societal and environmental impacts is likely to be more limited for phenotypic interventions (i) but higher for genetic interventions (ii and iii), especially for the ones which are transmissible to future generations (iii).

GENETIC ENGINEERING

The rapid advances in technology seen in the last decades, have raised the possibility of ‘radical enhancement’, defined by Nicholas Agar, ‘as the improvement of human attributes and abilities to levels that greatly exceed what is currently possible for human beings’ [24]. Genetic engineering offers the possibility of such an enhancement by providing humans a profound control over their own biology. Among other technologies, genetic engineering comprises genome editing (also called gene editing), a group of technologies with the ability to directly modify an organism’s DNA through a targeted intervention in the genome (e.g. insertion, deletion or replacement of specific genetic material) [25]. Genome editing is considered to achieve much greater precision than pre-existing forms of genetic engineering. It has been argued to be a revolutionary tool due to its efficiency, reducing cost and time. This technology is considered to have many applications for human health, in both preventing and tackling disease. Much of the ethical debate associated with this technology concerns the possible application of genome editing in the human germline, i.e. the genome that can be transmitted to following generations, be it from gametes, a fertilized egg or from first embryo divisions. There has been concern as well as enthusiasm on the potential of the technology to modify human germline genome to provide us with traits considered positive or useful (e.g. muscle strength, memory and intelligence) in the current and future environments.

Genetic engineering: therapy or enhancement and predictability of outcomes

To explore some of the possible implications of heritable interventions we will take as an example the editing (more specifically ‘deletion’ using CRISPR genome editing technology) of several base pairs of the CCR5 gene. Such intervention was practised in 2018 in two non-identical twin girls born in China. Loss of function mutations of the CCR5 had been previously shown to provide resistance to HIV. Therefore, the gene deletion would be expected to protect the twin baby girls from risk of transmission of HIV which could have occurred from their father (HIV-positive). However, the father had the infection kept under control and the titre of HIV virus was undetectable, which means that risk of transmission of HIV infection to the babies was negligible.

From an ethical ground, based on current acceptable practices, this case has been widely criticized by the scientific community beside being considered by many a case of human enhancement intervention rather than therapy. One of the questions this example helps illustrate is that the ethical boundary between a therapy that ‘corrects’ a disorder by restoring performance to a ‘normal’ scope, and an intervention that ‘enhances’ human ability outside the accepted ‘normal’ scope, is not always easy to draw. For the sake of argument, it could be assumed that therapy involves attempts to restore a certain condition of health, normality or sanity of the ‘natural’ condition of a specific individual. If we take this approach, the question is how health, normality and sanity, as well as natural per se, are defined, as the meaning of these concepts shift over time to accommodate social norms and cultural values of modern societies. It could be said that the difficulty of developing a conceptual distinction between therapy and enhancement has always been present. However, the potential significance of such distinction is only now, with the acceleration and impact of technological developments, becoming more evident.

Beyond ethical questions, a major problem of this intervention is that we do not (yet?) know exactly the totality of the effects that the artificial mutation of the CCR5 may have, at both the genetic and phenotypic levels. This is because we now know that, contrary to the idea of ‘one gene-one trait’ accepted some decades ago, a gene—or its absence—can affect numerous traits, many of them being apparently unrelated (a phenomenon also known as pleiotropy). That is, due to constrained developmental interactions, mechanisms and genetic networks, a change in a single gene can result in a cascade of multiple effects. In the case of CCR5, we currently know that the mutation offers protection against HIV infection, and also seems to increase the risk of severe or fatal reactions to some infectious diseases, such as the influenza virus. It has also been observed that among people with multiple sclerosis, the ones with CCR5 mutation are twice as likely to die early than are people without the mutation. Some studies have also shown that defective CCR5 can have a positive effect in cognition to enhance learning and memory in mice. However, it’s not clear if this effect would be translated into humans. The example serves to illustrate that, even if human enhancement with gene editing methods was considered ethically sound, assessing the totality of its implications on solid grounds may be difficult to achieve.

Genetic engineering and human evolution: large-scale impacts

Beyond providing the opportunity of enhancing human capabilities in specific individuals, intervening in the germline is likely to have an impact on the evolutionary processes of the human species raising questions on the scale and type of impacts. In fact, the use of large-scale genetic engineering might exponentially increase the force of ‘niche construction’ in human evolution, and therefore raise ethical and practical questions never faced by our species before. It has been argued that natural selection is a mechanism of lesser importance in the case of current human evolution, as compared to other organisms, because of advances in medicine and healthcare. According to such a view, among many others advances, natural selection has been conditioned by our ‘niche-construction’ ability to improve healthcare and access to clean water and food, thus changing the landscape of pressures that humans have been facing for survival. An underlying assumption or position of the current debate is that, within our human species, the force of natural selection became minimized and that we are somehow at the ‘end-point’ of our evolution. If this premise holds true, one could argue that evolution is no longer a force in human history and hence that any human enhancement would not be substituting itself to human evolution as a key driver for future changes.

However, it is useful to remember that, as defined by Darwin in his book ‘On the Origin of the Species’, natural selection is a process in which organisms that happen to be ‘better’ adapted to a certain environment tend to have higher survival and/or reproductive rates than other organisms. When comparing human evolution to human genetic enhancement, an acceptable position could be to consider ethically sound those interventions that could be replicated naturally by evolution, as in the case of the CCR5 gene. Even if this approach was taken, however, it is important to bear in mind that human evolution acts on human traits sometimes increasing and sometimes decreasing our biological fitness, in a constant evolutionary trade-off and in a contingent and/or neutral—in the sense of not ‘progressive’—process. In other worlds, differently from genetic human enhancement, natural selection does not ‘aim’ at improving human traits. Human evolution and the so-called genetic human enhancement would seem therefore to involve different underlying processes, raising several questions regarding the implications and risks of the latter.

But using genetic engineering to treat humans has been proposed far beyond the therapeutic case or to introduce genetic modifications known to already occur in nature. In particular, when looking into the views expressed on the balance between human evolution and genetic engineering, some argue that it may be appropriate to use genetic interventions to go beyond what natural selection has contributed to our species when it comes to eradicate vulnerabilities. Furthermore, when considering the environmental, ecological and social issues of contemporary times, some suggest that genetic technologies could be crucial tools to contribute to human survival and well-being. The possible need to ‘engineer’ human traits to ensure our survival could include the ability to allow our species to adapt rapidly to the rate of environmental change caused by human activity, for which Darwinian evolution may be too slow. Or, for instance, to support long-distance space travel by engineering resistance to radiation and osteoporosis, along with other conditions which would be highly advantageous in space.

When considering the ethical and societal merits of these propositions, it is useful to consider how proto-forms of enhancement has been approached by past human societies. In particular, it can be argued that humans have already employed—as part of our domestication/‘selective breeding’ of other animals—techniques of indirect manipulation of genomes on a relatively large scale over many millennia, albeit not on humans. The large-scale selective breeding of plants and animals over prehistoric and historic periods could be claimed to have already shaped some of our natural environment. Selective breeding has been used to obtain specific characteristics considered useful at a given time in plants and animals. Therefore, their evolutionary processes have been altered with the aim to produce lineages with advantageous traits, which contributed to the evolution of different domesticated species. However, differently from genetic engineering, domestication possesses inherent limitations in its ability to produce major transformations in the created lineages, in contrast with the many open possibilities provided by genetic engineering.

When considering the impact of genetic engineering on human evolution, one of questions to be considered concerns the effects, if any, that genetic technology could have on the genetic pool of the human population and any implication on its resilience to unforeseen circumstances. This underlines a relevant question associated with the difference between ‘health’ and biological fitness. For example, a certain group of animals can be more ‘healthy’—as domesticated dogs—but be less biologically ‘fit’ according to Darwin’s definition. Specifically, if such group of animals are less genetically diverse than their ancestors, they could be less ‘adaptable’ to environmental changes. Assuming that, the human germline modification is undertaken at a global scale, this could be expected to have an effect, on the distribution of genetically heritable traits on the human population over time. Considering that gene and trait distributions have been changing under the processes of evolution for billions of years, the impact on evolution will need to be assessed by analyzing which genetic alterations have been eventually associated with specific changes within the recent evolutionary history of humans. On this front, a key study has analyzed the implications of genetic engineering on the evolutionary biology of human populations, including the possibility of reducing human genetic diversity, for instance creating a ‘biological monoculture’. The study argued that genetic engineering will have an insignificant impact on human diversity, while it would likely safeguard the capacity of human populations to deal with disease and new environmental challenges and therefore, ensure the health and longevity of our species. If the findings of this study were considered consistent with other knowledge and encompassing, the impact of human genetic enhancements on the human genetic pool and associated impacts could be considered secondary aspects. However, data available from studies on domestication strongly suggests that domestication of both animals and plans might lead to not only decreased genetic diversity per se, but even affect patterns of variation in gene expression throughout the genome and generally decreased gene expression diversity across species. Given that, according to recent studies within the field of biological anthropology recent human evolution has been in fact a process of ‘self-domestication’, one could argue that studies on domestication could contribute to understanding the impacts of genetic engineering.

Beyond such considerations, it is useful to reflect on the fact that human genetic enhancement could occur on different geographical scales, regardless of the specific environment and geological periods in which humans are living and much more rapidly than in the case of evolution, in which changes are very slow. If this was to occur routinely and on a large scale, the implications of the resulting radical and abrupt changes may be difficult to predict and its impacts difficult to manage. This is currently highlighted by results of epigenetics studies, and also of the microbiome and of the effects of pollutants in the environment and their cumulative effect on the development of human and non-human organisms alike. Increasingly new evidence indicates a greater interdependence between humans and their environments (including other microorganisms), indicating that modifying the environment can have direct and unpredictable consequences on humans as well. This highlight the need of a ‘systems level’ approach. An approach in which the ‘bounded body’ of the individual human as a basic unit of biological or social action would need to be questioned in favour of a more encompassing and holistic unit. In fact, within biology, there is a new field, Systems Biology, which stresses the need to understand the role that pleiotropy, and thus networks at multiple levels—e.g. genetic, cellular, among individuals and among different taxa—play within biological systems and their evolution [46]. Currently, much still needs to be understood about gene function, its role in human biological systems and the interaction between genes and external factors such as environment, diet and so on. In the future if we do choose to genetically enhance human traits to levels unlikely to be achieved by human evolution, it would be crucial to consider if and how our understanding of human evolution enable us to better understand the implications of genetic interventions.

CONCLUSIONS

New forms of human enhancement are increasingly coming to play due to technological development. If phenotypic and somatic interventions for human enhancement pose already significant ethical and societal challenges, germline heritable genetic intervention, require much broader and complex considerations at the level of the individual, society and human species as a whole. Germline interventions associated with modern technologies are capable of much more rapid, large-scale impacts and seem capable of radically altering the balance of humans with the environment. We know now that beside the role genes play on biological evolution and development, genetic interventions can induce multiple effects (pleiotropy) and complex epigenetics interactions among genotype, phenotype and ecology of a certain environment. As a result of the rapidity and scale with which such impact could be realized, it is essential for ethical and societal debates, as well as underlying scientific studies, to consider the unit of impact not only to the human body but also to human populations and their natural environment (systems biology). An important practicable distinction between ‘therapy’ and ‘enhancement’ may need to be drawn and effectively implemented in future regulations, although a distinct line between the two may be difficult to draw.

In the future if we do choose to genetically enhance human traits to levels unlikely to be achieved by human evolution, it would be crucial to consider if and how our understanding of humans and other organisms, including domesticated ones, enable us to better understand the implications of genetic interventions. In particular, effective regulation of genetic engineering may need to be based on a deep knowledge of the exact links between phenotype and genotype, as well the interaction of the human species with the environment and vice versa.

For a broader and consistent debate, it will be essential for technological, philosophical, ethical and policy discussions on human enhancement to consider the empirical evidence provided by evolutionary biology, developmental biology and other disciplines.

Genetic Inequality: Human Genetic Engineering

As genetics allows us to turn the tide on human disease, it’s also granting the power to engineer desirable traits into humans. What limits should we create as this technology develops?

Genes influence health and disease, as well as human traits and behavior. Researchers are just beginning to use genetic technology to unravel the genomic contributions to these different phenotypes, and as they do so, they are also discovering a variety of other potential applications for this technology. For instance, ongoing advances make it increasingly likely that scientists will someday be able to genetically engineer humans to possess certain desired traits. Of course, the possibility of human genetic engineering raises numerous ethical and legal questions. Although such questions rarely have clear and definite answers, the expertise and research of bioethicists, sociologists, anthropologists, and other social scientists can inform us about how different individuals, cultures, and religions view the ethical boundaries for the uses of genomics. Moreover, such insights can assist in the development of guidelines and policies.

Testing for Traits Unrelated to Disease

Much of what we currently know about the ramifications of genetic self-knowledge comes from testing for diseases. Once disease genes were identified, it became much easier to make a molecular or cytogenetic diagnosis for many genetic conditions. Diagnostic testing supplies the technical ability to test presymptomatic, at-risk individuals and/or carriers to determine whether they will develop a specific condition. This sort of testing is a particularly attractive choice for individuals who are at risk for diseases that have available preventative measures or treatments, as well as people who might carry genes that have significant reproductive recurrence risks. Indeed, thanks to advances in single-cell diagnostics and fertilization technology, embryos can now be created in vitro; then, only those embryos that are not affected by a specific genetic illness can be selected and implanted in a woman’s uterus. This process is referred to as preimplantation genetic diagnosis.

For adult-onset conditions, ethical concerns have been raised regarding whether genetic testing should be performed if there is no cure for the disease in question. Many people wonder whether positive diagnosis of an impending untreatable disease will harm the at-risk individual by creating undue stress and anxiety. Interestingly, social science research has demonstrated that the answer to this question is both yes and no. It seems that if genetic testing shows that an individual is a carrier for a recessive disease, such as Tay-Sachs disease or sickle-cell anemia, this knowledge may have a negative impact on the individual’s well-being, at least in the short term (Marteau et al., 1992; Woolridge & Murray, 1988). On the other hand, if predictive testing for an adult-onset genetic disorder such as Huntington’s disease reveals that an at-risk individual will develop the disorder later in life, most patients report less preoccupation with the disease and a relief from the anxiety of the unknown (Taylor & Myers, 1997). For many people who choose to have predictive testing, gaining a locus of control by having a definitive answer is helpful. Some people are grateful for the opportunity to make life changes—for instance, traveling more, changing jobs, or retiring early—in anticipation of developing a debilitating condition later in their lives.

Of course, as genetic research advances, tests are continually being developed for traits and behaviors that are not related to disease. Most of these traits and behaviors are inherited as complex conditions, meaning that multiple genes and environmental, behavioral, or nutritional factors may contribute to the phenotype. Currently, available tests include those for eye color, handedness, addictive behavior, “nutritional” background, and athleticism. But does knowing whether one has the genetic background for these nondisease traits negatively affect one’s self-concept or health perception? Studies are now beginning to address this question. For example, one group of scientists performed genetic testing for muscle traits on a group of volunteers enrolled in a resistance-training program (Gordon et al., 2005). These tests looked for single-nucleotide polymorphisms that would tell whether an individual had a genetic predisposition for muscle strength, size, and performance. The investigators found that if the individuals did not receive affirmative genetic information regarding muscle traits, they credited the positive effects of the exercise program to their own abilities. However, those study participants who did receive positive test results were more likely to view the beneficial changes as out of their control, attributing any such changes to their genetic makeup. Thus, a lack of genetic predisposition for muscle traits actually gave subjects a sense of empowerment.

The results of the aforementioned study may be surprising to many people, as one major concern associated with testing for nondisease traits is the fear that those people who do not possess the genes for a positive trait may develop a negative self-image and/or inferiority complex. Another matter bioethicists often consider is that people may discover that they carry some genes associated with physiological or behavioral traits that are frequently perceived as negative. Moreover, many critics fear that the prevalence of these traits in certain ethnic populations could lead to prejudice and other societal problems. Thus, rigorous social science research by individuals from diverse cultural backgrounds is crucial to understanding people’s perceptions and establishing appropriate boundaries.

Building Better Athletes with Gene Doping


Figure 1: The double-muscled Belgian blue cow breed.Double muscled animals have an increase in muscle mass of up to 20% greater than normal animals. The increased muscle is due to the fact that these animals have a mutation in a specific gene that normally is involved in muscular hypertrophy.

Over the years, the desire for better sports performance has driven many trainers and athletes to abuse scientific research in an attempt to gain an unjust advantage over their competitors. Historically, such efforts have involved the use of performance-enhancing drugs that were originally meant to treat people with disease. This practice is called doping, and it frequently involved such substances as erythropoietin, steroids, and growth hormones. To control this drive for an unfair competitive edge, in 1999, the International Olympic Committee created the World Anti-Doping Agency (WADA), which prohibits the use of performance-enhancing drugs by athletes. WADA also conducts various testing programs in an attempt to catch those athletes who violate the anti-doping rules.

Today, WADA has a new hurdle to overcome—that of gene doping. This practice is defined as the nontherapeutic use of cells, genes, or genetic elements to enhance athletic performance. Gene doping takes advantage of cutting-edge research in gene therapy that involves the transfer of genetic material to human cells to treat or prevent disease (Well, 2008). Because gene doping increases the amount of proteins and hormones that cells normally make, testing for genetic performance enhancers will be very difficult, and a new race is on to develop ways to detect this form of doping.

The potential to alter genes to build better athletes was immediately realized with the invention of so-called “Schwarzenegger mice” in the late 1990s. These mice were given this nickname because they were genetically engineered to have increased muscle growth and strength. The goal in developing these mice was to study muscle disease and reverse the decreased muscle mass that occurs with aging. Interestingly, the Schwarzenegger mice were not the first animals of their kind; that title belongs to Belgian Blue cattle (Figure 1), an exceptional breed known for its enormous muscle mass. These animals, which arose via selective breeding, have a mutated and nonfunctional copy of the myostatin gene, which normally controls muscular development. Without this control, the cows’ muscles never stop growing. In fact, Belgian Blue cattle get so large that most females of the breed cannot give natural birth, so their offspring have to be delivered by cesarean section. Schwarzenegger mice differ from these cattle in that they highlight scientists’ newfound ability to induce muscle development through genetic engineering, which brings up the evident advantages for athletes. But does conferring one desirable trait create other, more harmful consequences? Are gene doping and other forms of genetic engineering something worth exploring, or should we, as a society, decide that manipulation of genes for non disease purposes is unethical?

Creating Designer Babies

Genetic testing also harbors the potential for yet another scientific strategy to be applied in the area of eugenics, or the social philosophy of promoting the improvement of inherited human traits through intervention. In the past, eugenics was used to justify practices including involuntary sterilization and euthanasia. Today, many people fear that preimplantation genetic diagnosis may be perfected and could technically be applied to select specific nondisease traits (rather than eliminate severe disease, as it is currently used) in implanted embryos, thus amounting to a form of eugenics. In the media, this possibility has been sensationalized and is frequently referred to as creation of so-called “designer babies,” an expression that has even been included in the Oxford English Dictionary. Although possible, this genetic technology has not yet been implemented; nonetheless, it continues to bring up many heated ethical issues.

Trait selection and enhancement in embryos raises moral issues involving both individuals and society. First, does selecting for particular traits pose health risks that would not have existed otherwise? The safety of the procedures used for preimplantation genetic diagnosis is currently under investigation, and because this is a relatively new form of reproductive technology, there is by nature a lack of long-term data and adequate numbers of research subjects. Still, one safety concern often raised involves the fact that most genes have more than one effect. For example, in the late 1990s, scientists discovered a gene that is linked to memory. Modifying this gene in mice greatly improved learning and memory, but it also caused increased sensitivity to pain, which is obviously not a desirable trait. Beyond questions of safety, issues of individual liberties also arise. For instance, should parents be allowed to manipulate the genes of their children to select for certain traits when the children themselves cannot give consent? Suppose a mother and father select an embryo based on its supposed genetic predisposition to musicality, but the child grows up to dislike music. Will this alter the way the child feels about its parents, and vice versa? Finally, in terms of society, it is not feasible for everyone to have access to this type of expensive technology. Thus, perhaps only the most privileged members of society will be able to have “designer children” that possess greater intelligence or physical attractiveness. This may create a genetic aristocracy and lead to new forms of inequality.

At present, these questions and conjectures are purely hypothetical, because the technology needed for trait selection is not yet available. In fact, such technology may be impossible, considering that most traits are complex and involve numerous genes. Still, contemplation of these and other issues related to genetic engineering is important should the ability to create genetically enhanced humans ever arise.

Genetically modified humans: the X-Men of scientific research

The CRISPR/Cas9 system has been revolutionary in the world of genetic research. However, as genetic engineering moves into human applications, it’s now time to ask: what benefits can this bring? And, how far is too far when it comes to altering the human genome?

Genome editing techniques have been around for decades; in 1973, the first transgenic organism was created by the insertion of antibiotic resistance genes into Escherichia coli, which was quickly followed by the first transgenic animal – a mouse – a year later. Since then, it has been applied across all areas of biology, from creating bacteria that could break down crude oil to increasing the shelf life of tomatoes.

However, it was the introduction of the CRISPR/Cas9 system in 2012 that kick-started the rapid development of gene editing technology into the widely practiced technique that it is today. Thousands of papers on CRISPR are published each year, with the rate increasing annually. It seems that the applications of CRISPR know no bounds, with geneticists everywhere keen to apply the technique to anything and everything.

With use on the bacterial genome becoming old hat, researchers are turning to human use; asking how they can use this technology for a therapeutic advantage. Shifting the focus of research to the treatment of genetic diseases, laboratory advances are being made for multiple disorders and some are already being put to clinical use.

Although becoming a reality, the alteration of human DNA remains something seemingly fictional. Be it Professor X, Deadpool or Scarlet Witch, those with modified DNA or ‘mutants’ are still associated with the superheroes of well-known comic books and films. Currently, the use of CRISPR in humans is purely therapeutic, fixing genetic mutations rather than creating them; however, such therapies are giving individuals abilities above those that the DNA they were born with gave them. They are becoming the first genetically modified humans; individuals whose DNA is being altered in order to improve their quality of life.

With trials at a variety of stages, from in vitro to animal models to early clinical use, the therapeutic use of CRISPR in humans is likely to increase as more and more successful and beneficial effects are demonstrated. Edits in the genome are giving these individuals ‘powers’ as they do to the superheroes of fiction, if on a significantly smaller scale. Though unlikely to save the world, to an individual with an illness, such abilities may seem super if they can save their life.

The power of invisibility

In a healthy individual, the immune system makes for a formidable opponent to infection. As the body’s first line of defense against bacteria, parasites and viruses, it enables us to survive while in a world surrounded by pathogens. However, when it comes to patients who have undergone a transplant, it quickly turns to the dark side, acting as the villain for patients and doctors alike. The transplanted cells are perceived as foreign, initiating an immune response that leads to transplant rejection.

Currently there is no 100% effective way to prevent rejection. When matching donors to the recipient, doctors aim to reduce the likelihood of this complication by ensuring that the pair are as histologically compatible as possible and by administering immunosuppressive drugs. Despite best efforts, acute rejection is something that occurs to some degree in almost all transplants, the exception being those between identical twins, unless true immunosuppression has been achieved.

However, the immunosuppression itself can then cause further problems. “We can administer drugs that suppress immune activity and make rejection less likely. Unfortunately, these immunosuppressants leave patients more susceptible to infection and cancer,” explained Sonja Schrepfer from the University of California, San Francisco (UCSF; CA, USA).

Stem cell transplantation is one area where rejection is a key issue. At one time, with the introduction of the induced pluripotent stem cell (iPSC), it appeared that the problem of rejection was solved. You would think that, as these stem cells were created from the intended recipient’s own cells, they would not be perceived as foreign; the body would recognize the cells as being their own and no immune response would be triggered. Unfortunately, the results did not pan out that way.

Schrepfer and Deuse in the lab.

There are many issues with iPSC technology, but the biggest hurdles are quality control and reproducibility. We don’t know what makes some cells amenable to reprogramming, but most scientists agree it can’t yet be reliably done,” commented Tobias Deuse (UCSF). “Most approaches to individualized iPSC therapies have been abandoned because of this.

In an attempt to overcome these issues, Deuse, Schrepfer and their team at UCSF created a universal iPSC, using CRISPR/Cas9 genome editing to alter three genes and make the cells ‘invisible’ to the immune system.

The CRISPR-controlled knockdown of two genes that code for the major histocompatibility complex class I and II family of proteins and a vector-mediated increase of the gene coding for the CD47 surface protein meant that the donor cells were not rejected by the recipient. First demonstrated by transplanting mouse iPSCs into mismatched, healthy mice and then again by transplanting human iPSCs into humanized mice, the researchers found that the cells did not elicit any form of immune response and were able to evade the radar of the immune system.

This is the first time anyone has engineered cells that can be universally transplanted and can survive in immunocompetent recipients without eliciting an immune response,” commented Deuse. “Our technique solves the problem of rejection of stem cells and stem cell-derived tissues and represents a major advance for the stem cell therapy field.

By granting the power of invisibility, CRISPR technology holds the potential to improve response rates to transplants and to reduce rejection. With early applications in iPSCs, expanding to other transplant areas may not be too far behind. Coupled with advances in 3D printing of organs, this application of CRISPR may result in an ‘invisible’ kidney, lung or heart.

The power of strength

An almost cliché trope of the superhero is the extreme strength they are capable of; whether it’s Superman lifting cars or the Hulk smashing his way through buildings, every good hero has the power to bench-press more than your average Joe. Though currently used CRISPR techniques aren’t being utilized to enhance a healthy individual’s strength, they do have potential to restore it to those who are lacking.

Duchenne muscular dystrophy (DMD) is an X-linked, monogenic disorder where mutations in the DMD gene on the X chromosome prevent the production of the dystrophin protein in muscles. Displaying mendelian inheritance, it is a disorder that predominantly affects males, with females more likely to be carriers. The mutation causes premature termination of translation, resulting in a loss of the production of the protein dystrophin, without which muscles are weak, fragile and can be easily damaged.

Being caused by a single gene makes DMD a prime target for gene therapies. However, the DMD gene is the second largest gene known, with 2.6 million base pairs, making it unsuitable for vector-mediated insertion of a nonmutated version. In using the CRISPR/Cas9 technology to correct the mutation rather than replace it, a team from the University of Texas (UT) Southwestern (TX, USA) demonstrated that a correction of the mutation in a mouse zygote led to improved muscle function when the mouse was 1 month old.

Since their first CRISPR study, the team have improved their strategy and demonstrated the success of gene editing to restore dystrophin synthesis both in vitro and in vivo. Using 3D engineered heart muscle, they found that a single cut was enough to skip the defective exon, resulting in the restoration of dystrophin protein expression and muscle function. “We found that correcting less than half of the cardiomyocytes (heart muscle cells) was enough to rescue cardiac function to near-normal levels in human-engineered heart tissue,” explained Chengzu Long (UT Southwestern), the study’s lead author.

The UT Southwestern team then moved onto in vivo canine studies, using their single-cut CRISPR editing technique to target a mutation on exon 51, resulting in a restoration of dystrophin to 92% of its normal levels in the heart and 58% in the diaphragm.

Our strategy is different from other therapeutic approaches for DMD because it edits the mutation that causes the disease and restores normal expression of the repaired dystrophin,” commented Leonela Amoasii, lead author of the canine study. “But we have more to do before we can use this clinically. 

In their most recent work, the research group have demonstrated the ability of the CRISPR/Cas9 system to correct the deletion mutation of exon 44 of the DMD gene in mice and human iPSC-derived cardiomyocytes. They found that when targeting this section of the gene, a different region to that targeted in their previous studies, the standard 1-to-1 ratio of Cas9 and guide RNA was not as effective.

Dystrophin (red) restoration shown in a CRISPR edited DMD-affected heart muscle cell (right) relative to unedited cell (left).

The newly developed method involving an altered ratio boosted the efficiency of the gene editing, results that could have implications across the field of gene therapy and not just DMD. “As we test CRISPR on other defective parts of the dystrophin gene, it may be important to tweak our formulas for optimal results,” commented Eric Olson (UT Southwestern), study leader and director of the research group. “This new insight further facilitates the use of CRISPR as a therapy for Duchenne and perhaps a number of other diseases”.

The power of resistance

When it comes to CRISPR, perhaps the most dramatic and controversial advancement was the birth of the so-called ‘CRISPR twins’. Previously, genome editing had been limited to altering somatic cells, meaning that any edits made would not be heritable. The twin girls, born November 2018, marked the start of germline edits where the effects of the CRISPR edits will not only affect their lives but also those of their future generations.

He Jiankui from the Southern University of Science and Technology (Shenzhen, China) and his research team used CRISPR technology to delete the CCR5 gene, with an overall aim of rendering the resultant offspring resistant to HIV, smallpox, and cholera.

Announcing his results in a YouTube video, Jiankui stated that “gene surgery is another IVF advancement” and emphasized that the research was for the benefit of families who could not have children otherwise and therefore “need this technology”. The positive and wholesome message given by Jiankui did not have the reception intended, with fellow scientists being shocked by the experiment and skeptical of his family-centric approach, many calling the work selfish and fame-driven; the Center for Genetics and Society (CA, USA) labeled the work as “a grave abuse of human rights”.

Jiankui first announced the study in a YouTube video.

Resistance to some of the world’s deadliest diseases is a significant medical advantage, although in today’s world, seemingly unnecessary. The benefits of treatment options currently available significantly outweigh the risks of the CRISPR procedure. However, further research has shown that immunity to disease is unlikely to be the only power granted by this edit. Aside from the as-yet-unknown off-target effects, the editing of the CCR5 gene may also have enhanced their learning and memory. In murine models, deleting the gene has been shown to significantly improve memory and can make the animals smarter.

The link between CCR5 and cognition has been known since 2016, when a study revealed that it could act as a suppressor for cortical plasticity as well as hippocampal learning and memory [15]. Upon hearing about the twins, author of the 2016 study Alcino J Silva (University of California, Los Angeles; CA, USA) commented, “the simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins”. The question remains as to the extent of the effect which, at this stage, is impossible to predict and, according to Silva, “that is why it should not be done”.

In his announcement video, Jiankui agreed that the technique should be used for healing and not for enhancing IQ. Despite this suggestion that there was no initial intent to improve the twin’s cognitive abilities, Jiankui made no attempt to collaborate with experts to discuss the potential effect of CCR5 on cognition and, while admitting he knew of the study, said that it “needs more independent verification”.

Since the birth of the twins, new research has once again shown the effect that suppressing CCR5 can have on the brain, this time demonstrating it to be a therapeutic target to improve recovery from stroke or traumatic brain injury [17]. The study also highlighted a link between the gene and everyday intelligence, with those who are missing at least one copy of the gene appearing to go further in school.

The backlash that occurred when Jiankui announced his study has halted the editing of germline cells for the foreseeable future. The view of Jiankui’s work as reckless has led to the formation of a group of experts by the World Health Organization, tasked with setting out guidelines for future CRISPR studies and evaluating the ethics of its use. Scientists from across the world, including CRISPR co-inventor Feng Zhang, have called for a global moratorium on germline editing. This would include a freeze on any ongoing germline editing projects until an international framework for practice can be outlined.

However, at the summit where Jiankui first presented his results, there was a consensus that such use for gene editing was inevitable. Dean of Harvard Medical School (MA, USA), George Daley, told the conference, “the fact that the first instance of human germline editing came forward as a misstep should not let us stick our neck in the sand. It’s time to move forward from [debates on] ethical permissibility to outline the path to clinical translation”.

It is unknown what the full effect of the gene surgery will be, only time will tell as the twins grow and develop. If predictions hold true, this case will have shown what is possible and will likely be the inspiration for future work; Pandora’s box of potential has been well and truly opened and it may be too late to close it.

The power to have it all?

It is undeniable that the therapeutic use of CRISPR will become mainstream in the not-so-distant future. As more applications are made available, somatic gene surgery will likely become first line for the treatment of genetic disorders.

However, once the technology is available, what is there to stop geneticists following the tropes of comics and going full ‘mad-scientist’? The CRISPR-twins story could be the first of many seemingly unnecessary genetic modifications that begin to occur as the technology becomes more controllable and new potential targets are identified. As advances occur, perhaps the question scientists ask themselves will change from, could we do that? to, should we do that?

It may be a stretch and seemingly ridiculous now, but as the CRISPR technology advances and the range of potential applications widens, it could lead to us asking one question; what would your superpower be?

Human, Social, and Environmental Impacts of Human Genetic Engineering

Introduction

Human genetic engineering relies heavily on science and technology. It was developed to help end the spread of diseases. With the advent of genetic engineering, scientists can now change the way genomes are constructed to terminate certain diseases that occur as a result of genetic mutation. Today genetic engineering is used in fighting problems such as cystic fibrosis, diabetes, and several other diseases. Another deadly disease now being treated with genetic engineering is the “bubble boy” disease (Severe Combined Immunodeficiency). This is a clear indication that genetic engineering has the potential to improve the quality of life and allow for longer life span.

Clearly, one of the greatest benefits of this field is the prospect of helping cure illness and diseases in unborn children. Having a genetic screening with a fetus can allow for treatment of the unborn. Overtime this can impact the growing spread of diseases in future generations.

However, these benefits are not without peril. Human genetic engineering is a development that people are either very passionate about or opposed to completely. This article gives a brief account on the effect of this principle on the biosphere together with several controversial issues that accompany the acceptance of this technology. The manuscript has been prepared by using information from peer reviewed journals indexed in pubmed in the period of 2000 to 2015.

Effects on the Environment

Although the positive impacts of this field could be enormous, there are many questions raised that needs to be answered. New organisms created by genetic engineering could present an ecological problem. One cannot predict the changes that a genetically engineered species would make on the environment. The release of a new genetically engineered species would also have the possibility of causing an imbalance in the ecology of a region just exotic species would do. An accident or an unknown result could cause several problems. An accident in engineering the genetics of a virus or bacteria for example could result in a stronger type, which could cause a serious epidemic when released. This could be fatal in human genetic engineering creating problems ranging from minor medical problems, to death.

Effects on Human

Looking at the fact that genetic engineering employs viral vector that carries functional gene inside the human body; the repercussion are still unknown. There are no clues as to where functional genes are being placed. They may even replace the important genes, instead of mutated genes. Thus, this may lead to another health condition or disease to human. Also, as defective genes are replaced with functional gene, then it is expected that there will be a reduction in genetic diversity and if human beings will have identical genomes, the population as a whole will be susceptible to virus or any form of diseases.

Genetic engineering could also create unknown side effects or outcomes. Certain changes in a plant or animal could cause unpredicted allergic reactions in some people which, in its original form, did not occur. Other changes could result into the toxicity of an organism to humans or other organisms.

Antibiotic Resistance

Genetic engineering often uses genes for antibiotic resistance as “selectable markers.” Early in the engineering process, these markers help identify cells that have taken up foreign genes. Although they have no further use, the genes continue to be expressed in plant tissues. Most genetically engineered plant foods carry fully functioning antibiotic-resistance genes.

The presence of antibiotic-resistance genes in foods could have lethal effects. Therefore, eating these foods could reduce the effectiveness of antibiotics to fight disease when these antibiotics are taken with meals. More so, the resistance genes could be transferred to human or animal pathogens, making them impervious to antibiotics. If transfer were to occur, it could aggravate the already serious health problem of antibioticresistant disease organisms.

Ethical and Social Issues

“Playing God” has become a strong argument against genetic engineering. Several issues have also been raised as regards the acceptance of this technology. These concerns range from ethical issues to lack of knowledge on the effects genetic engineering may have. One major concern is that once an altered gene is placed in an organism, the process cannot be reversed. Public reaction to the use of rDNA in genetic engineering has been mixed. The production of medicines through the use of genetically altered organisms has generally been welcomed. However, critics of rDNA fear that disease-producing, organisms used in some rDNA experiments might develop extremely infectious forms that could cause worldwide epidemics.

As more human genes are being used in non-human organisms to create new forms of life that are genetically partly human, new ethical questions arise. For instance, what percentage of human genes does an organism have to contain before it is considered human and how many human genes would a green pepper for example have to contain before it can be eaten without qualms. Human genes are now being inserted into tomatoes and peppers to make them grow faster. This suggests that one can now be a vegetarian and a cannibal at the same time. For meat eaters, the same question could be posed about eating pork with human genes. What about the mice that have been genetically engineered to produce human sperm. The question is ‘what psychological effect would it pose on the offspring?

Critics have questioned the safety of genetically engineered bovine somatotropin (BST) to increase the milk yield of dairy cows (BST) for both the cows that are injected with it and the humans who drink the resulting milk; owing to the fact that it increases a cow’s likelihood of developing mastitis, or infection of the udder, and it also makes cows more susceptible to infertility and lameness.

Transgenic plants also present controversial issues. Allergens can be transferred from one food crop to another through genetic engineering. Another concern is that pregnant women eating genetically modified products may endanger their offspring by harming normal fetal development and altering gene expression.

In 2002 the National Academy of Sciences released a report calling for a legal ban on human cloning. The report concluded that the high rate of health problems in cloned animals suggests that such an effort in humans would be highly dangerous for the mother and developing embryo and is likely to fail. Beyond safety, the possibility of cloning humans also raises a variety of social issues like the psychological issues that would result for a cloned child who is the identical twin of his or her parent.

Another frightening scenario is the destructive use of genetic engineering. Terrorist groups or armies could develop more powerful biological weaponry. These weapons could be resistant to medicines, or even targeted at people who carry certain genes. Genetically engineered organisms used for biological weapons might also reproduce faster, which would create larger quantities in shorter periods of time, increasing the level of devastation.

Conclusion

Despite all of these current concerns, the potential for genetic engineering is tremendous. However, further testing and research will be required to educate society on the pros and cons of genetic engineering. There is no doubt that this technology will continue to present intriguing and difficult challenges for 21st century scientists and ethicists, and education and meaningful, respectful discourse are just the starting point of what is required to tackle such complex ethical issues. With the newfound breakthroughs in cloning, the capabilities of changing human characteristics are unpredictable. We can then anticipate intense cross-disciplinary debate and discussion as new life forms are emanating through science and medicine.

Experts debate: Are we playing with fire when we edit human genes?

Perspectives on gene editing

Harvard researchers, others share their views on key issues in the field

Medicine is at a turning point, on the cusp of major change as disruptive technologies such as gene, RNA, and cell therapies enable scientists to approach diseases in new ways. The swiftness of this change is being driven by innovations such as CRISPR gene editing, which makes it possible to correct errors in DNA with relative ease.

Progress in this field has been so rapid that the dialogue around potential ethical, societal, and safety issues is scrambling to catch up.

This disconnect was brought into stark relief at the Second International Summit on Human Genome Editing, held in Hong Kong in November, when exciting updates about emerging therapies were eclipsed by a disturbing announcement. He Jiankui, a Chinese researcher, claimed that he had edited the genes of two human embryos, and that they had been brought to term.

There was immediate outcry from scientists across the world, and He was subjected to intense social pressure, including the removal of his affiliations, for having allegedly disregarded ethical norms and his patients’ safety.

Yet as I. Glenn Cohen, faculty director of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School, has said, gene editing comes in many varieties, with many consequences. Any deep ethical discussion needs to take into account those distinctions.

Human genome editing: somatic vs. germline

The germline editing He claimed to have carried out is quite different from the somatic gene therapies that are currently changing the frontiers of medicine. While somatic gene editing affects only the patient being treated (and only some of his or her cells), germline editing affects all cells in an organism, including eggs and sperm, and so is passed on to future generations. The possible consequences of that are difficult to predict.

Somatic gene therapies involve modifying a patient’s DNA to treat or cure a disease caused by a genetic mutation. In one clinical trial, for example, scientists take blood stem cells from a patient, use CRISPR techniques to correct the genetic mutation causing them to produce defective blood cells, then infuse the “corrected” cells back into the patient, where they produce healthy hemoglobin. The treatment changes the patient’s blood cells, but not his or her sperm or eggs.

Germline human genome editing, on the other hand, alters the genome of a human embryo at its earliest stages. This may affect every cell, which means it has an impact not only on the person who may result, but possibly on his or her descendants. There are, therefore, substantial restrictions on its use.

Germline editing in a dish can help researchers figure out what the health benefits could be, and how to reduce risks. Those include targeting the wrong gene; off-target impacts, in which editing a gene might fix one problem but cause another; and mosaicism, in which only some copies of the gene are altered. For these and other reasons, the scientific community approaches germline editing with caution, and the U.S. and many other countries have substantial policy and regulatory restrictions on using germline human genome editing in people.

But many scientific leaders are asking: When the benefits are believed to outweigh the risks, and dangers can be avoided, should science consider moving forward with germline genome editing to improve human health? If the answer is yes, how can researchers do so responsibly?

CRISPR pioneer Feng Zhang of the Broad Institute of Harvard and MIT responded immediately to He’s November announcement by calling for a moratorium on implanting edited embryos in humans. Later, at a public event on “Altering the Human Genome” at the Belfer Center at Harvard Kennedy School (HKS), he explained why he felt it was important to wait:

“The moratorium is a pause. Society needs to figure out if we all want to do this, if this is good for society, and that takes time. If we do, we need to have guidelines first so that the people who do this work can proceed in a responsible way, with the right oversight and quality controls.”

Somatic gene editing compared to germline gene editing.Graphic by Judy Blomquist/Harvard Staff

Professors at the University’s schools of medicine, law, business, and government saw He’s announcement as a turning point in the discussion about heritable gene therapies and shared their perspectives on the future of this technology with the Gazette.

Here are their thoughts, issue by issue:

Bioethics

Aside from the safety risks, human genome editing poses some hefty ethical questions. For families who have watched their children suffer from devastating genetic diseases, the technology offers the hope of editing cruel mutations out of the gene pool. For those living in poverty, it is yet another way for the privileged to vault ahead. One open question is where to draw the line between disease treatment and enhancement, and how to enforce it, considering differing attitudes toward conditions such as deafness.

Robert Truog, director of the Center for Bioethics at Harvard Medical School (HMS), provided context:

“This question is not as new as it seems. Evolution progresses by random mutations in the genome, which dwarf what can be done artificially with CRISPR. These random mutations often cause serious problems, and people are born with serious defects. In addition, we have been manipulating our environment in so many ways and exposing ourselves to a lot of chemicals that cause unknown changes to our genome. If we are concerned about making precise interventions to cure disease, we should also be interested in that.

“To me, the conversation around Dr. He is not about the fundamental merits of germline gene editing, which in the long run will almost certainly be highly beneficial. Instead, it’s about the oversight of science. The concern is that with technologies that are relatively easy to use, like CRISPR, how does the scientific community regulate itself? If there’s a silver lining to this cloud, I think it is that the scientific community did pull together to be critical of this work, and took the responsibility seriously to use the tools available to them to regulate themselves.”

Business

When asked what the implications of He’s announcement are for the emerging field of precision medicine, Richard Hamermesh, faculty co-chair of the Harvard Business School/Kraft Precision Medicine Accelerator, said:

“Before we start working on embryos, we have a long way to go, and civilization has to think long and hard about it. There’s no question that gene editing technologies are potentially transformative and are the ultimate precision medicine. If you could precisely correct or delete genes that are causing problems — mutating or aberrant genes — that is the ultimate in precision. It would be so transformative for people with diseases caused by a single gene mutation, like sickle cell anemia and cystic fibrosis. Developing safe, effective ways to use gene editing to treat people with serious diseases with no known cures has so much potential to relieve suffering that it is hard to see how anyone could be against it.

“There is also commercial potential and that will drive it forward. A lot of companies are getting venture funding for interesting gene therapies, but they’re all going after tough medical conditions where there is an unmet need — [where] nothing is working — and they’re trying to find gene therapies to cure those diseases. Why should we stop trying to find cures?

“But anything where you’re going to be changing human embryos, it’s going to take a long time for us to figure out what is appropriate and what isn’t. That has to be done with great care in terms of ethics.”

Medicine

George Q. Daley  is dean of HMS, the Caroline Shields Walker Professor of Medicine, and a leader in stem cell science and cancer biology. As a spokesperson for the organizing committee of the Second International Summit on Human Genome Editing, he responded swiftly to He’s announcement in Hong Kong. Echoing those remarks, he said:

“It’s time to formulate what a clinical path to translation might look like so that we can talk about it. That does not mean that we’re ready to go into the clinic — we are not. We need to specify what the hurdles would be if one were to move forward responsibly and ethically. If you can’t surmount those hurdles, you don’t move forward.

“There are stark distinctions between editing genes in an embryo to prevent a baby from being born with sickle cell anemia and editing genes to alter the appearance or intelligence of future generations. There is a whole spectrum of considerations to be debated. The prospect includes an ultimate decision that we not go forward, that we decide that the benefits do not outweigh the costs.”

Asked how to prevent experiments like He’s while preserving academic freedom, Daley replied:

“For the past 15 years, I have been involved in efforts to establish international standards of professional conduct for stem cell research and its clinical translation, knowing full well that there could be — and has been — a growing number of independent practitioners directly marketing unproven interventions to vulnerable patients through the internet. We advocated so strongly for professional standards in an attempt to ward off the risks of an unregulated industry. Though imperfect, our efforts to encourage a common set of professional practices have been influential.

“You can’t control rogue scientists in any field. But with strongly defined guidelines for responsible professional conduct in place, such ethical violations like those of Dr. He should remain a backwater, because most practitioners will adhere to generally accepted norms. Scientists have a responsibility to come together to articulate professional standards and live by them. One has to raise the bar very high to define what the standards of safety and efficacy are, and what kind of oversight and independent judgment would be required for any approval.

“We have called for an ongoing international forum on human genome editing, and that could take many shapes. We’ve suggested that the national academies of more countries come together — the National Academy of Sciences in the U.S. and the Royal Society in the U.K. are very active here — because these are the groups most likely to have the expertise to convene these kinds of discussions and keep them going.”

Law

Cohen, speaking to the legal consequences of germline human genome editing, said:

“I think we should slow down in our reaction to this case. It is not clear that the U.S. needs to react to Dr. He’s announcement with regulation. The FDA [Food and Drug Administration] already has a strong policy on germline gene editing in place. A rider in the Consolidated Appropriations Act of 2016 — since renewed — would have blocked the very same clinical application of human germline editing He announced, had it been attempted in the U.S.

“The scientific community has responded in the way I’d have liked it to. There is a difference between ‘governance’ and ‘self-governance.’ Where government uses law, the scientific community uses peer review, public censure, promotions, university affiliations, and funding to regulate themselves. In China, in Dr. He’s case, you have someone who’s (allegedly) broken national law and scientific conventions. That doesn’t mean you should halt research being done by everyone who’s law-abiding.

“Public policy or ethical discussion that’s divorced from how science is progressing is problematic. You need to bring everyone together to have robust discussions. I’m optimistic that this is happening, and has happened. It’s very hard to deal with a transnational problem with national legislation, but it would be great to reach international consensus on this subject. These efforts might not succeed, but ultimately they are worth pursuing.”

Science

Professor Kevin Eggan of Harvard’s Department of Stem Cell and Regenerative Biology said, “The question we should focus on is: Will this be safe and help the health of a child? Can we demonstrate that we can fix a mutation that will cause a terrible health problem, accurately and without the risk of harming their potential child? If the answer is yes, then I believe germline human genome editing is likely to gain acceptance in time.

“There could be situations where it could help a couple, but the risks of something going wrong are real. But at this point, it would be impossible to make a risk-benefit calculation in a responsible manner for that couple. Before we could ever move toward the clinic, the scientific community must come to a consensus on how to measure success, and how to measure off-target effects in animal models.

“Even as recently as this past spring and fall, the results of animal studies using CRISPR — the same techniques Dr. He claimed to have used — generated a lot of confusion. There is disagreement about both the quality of the data and how to interpret it. Until we can come to agreement about what the results of animal experiments mean, how could we possibly move forward with people?

“As happened in England with mitochondrial replacement therapy, we should be able to come to both a scientific and a societal consensus of when and how this approach should be used. That’s missing.”

According to Catherine Racowsky, professor of obstetrics, gynecology and reproductive biology at Brigham and Women’s Hospital, constraints on the use of embryos in federally funded research pose barriers to studying the risks and benefits of germline editing in humans. She added:

“Until the work is done, carefully and with tight oversight, to understand any off-target effects of replacing or removing a particular gene, it is inappropriate to apply the technology in the clinical field. My understanding of Dr. He’s case is that there wasn’t a known condition in these embryos, and by editing the genes involved with HIV infection, he could also have increased the risks of susceptibility to influenza and West Nile viruses.

“We need a sound oversight framework, and it needs to be established globally. This is a technology that holds enormous promise, and it is likely to be applied to the embryo, but it should only be applied for clinical purposes after the right work has been done. That means we must have consensus on what applications are acceptable, that we have appropriate regulatory oversight, and, perhaps most importantly, that it is safe. The only way we’re going to be able to determine that these standards are met is to proceed cautiously, with reassessments of the societal and health benefits and the risks.”

Asked about public dialogue around germline human genome editing, George Church, Robert Winthrop Professor of Genetics at HMS, said:

“With in vitro fertilization (IVF), ‘test tube babies’ was an intentionally scary term. But after Louise Brown, the first IVF baby, was born healthy 40 years ago, attitudes changed radically. Ethics flipped 180 degrees, from it being a horrifying idea to being unacceptable to prevent parents from having children by this new method. If these edited twins are proven healthy, very different discussions will arise. For example, is a rate of 900,000 deaths from HIV infection per year a greater risk than West Nile virus, or influenza? How effective is each vaccine?”

Science, technology, and society

Sheila Jasanoff, founding director of the Science, Technology, and Society program at HKS, has been calling for a “global observatory” on gene editing, an international network of scholars and organizations dedicated to promoting exchange across disciplinary and cultural divides. She said:

“The notion that the only thing we should care about is the risk to individuals is very American. So far, the debate has been fixated on potential physical harm to individuals, and not anything else. This is not a formulation shared with other countries in the world, including practically all of Europe. Considerations of risk have equally to do with societal risk. That includes the notion of the family, and what it means to have a ‘designer baby.’

“These were not diseased babies Dr. He was trying to cure. The motivation for the intervention was that they live in a country with a high stigma attached to HIV/AIDS, and the father had it and agreed to the intervention because he wanted to keep his children from contracting AIDS. AIDS shaming is a fact of life in China, and now it won’t be applied to these children. So, are we going to decide that it’s OK to edit as-yet-to-be children to cater to this particular idea of a society?

“It’s been said that ‘the genie is out of the bottle’ with germline human genome editing. I just don’t think that’s true. After all, we have succeeded in keeping ‘nuclear’ inside the bottle. Humanity doesn’t lack the will, intelligence, or creativity to come up with ways for using technology for good and not ill.

“We don’t require students to learn the moral dimensions of science and technology, and that has to change. I think we face similar challenges in robotics, artificial intelligence, and all kinds of frontier fields that have the potential to change not just individuals but the entirety of what it means to be a human being.

“Science has this huge advantage over most professional thought in that it has a universal language. Scientists can hop from lab to lab internationally in a way that lawyers cannot because laws are written in many languages and don’t translate easily. It takes a very long time for people to understand each other across these boundaries. A foundational concept for human dignity? It would not be the same thing between cultures.

“I would like to see a ‘global observatory’ that goes beyond gene editing and addresses emerging technologies more broadly.”

How genetic engineering will reshape humanity

A book excerpt and interview with Jamie Metzl, author of “Hacking Darwin”

NEW GENETIC technologies are exhilarating and terrifying. Society might overcome diseases by tweaking individual genomes or selecting specific embryos to avoid health problems. But it may also give rise to “superhumans” who are optimised for certain characteristics (like intelligence or looks) and exacerbate inequalities in society.

What is certain is that people will be able to make decisions about their lives in ways that were impossible in the past, when we relied more on random evolution than deliberation. In the words of Jamie Metzl, we are “Hacking Darwin,” the title of his latest book. It is a thoughtful romp through new genetic technologies, with insights on what it means for individuals, society and even great-power politics.

The theme draws together discrete strands of Mr Metz’s diverse background. He’s worked for the United Nations on humanitarian issues in Cambodia and served on America’s National Security Council under President Bill Clinton. He’s been an executive at a biotechnology company, a partner at large investment fund in New York and a candidate for Congress from Missouri. But perhaps even more relevantly, he is the author of two sci-fi novels on genetics, “Genesis Code” and “Eternal Sonata.”

As part of The Economist’s Open Future project, we asked Mr Metzl about genetic engineering, inequality and the new “liberal agenda”. Below the interview is an excerpt from his book, on the history of eugenics.

* * *

The Economist: What are the ways in which people are able to “hack Darwin” today and over the next 15 years or so?

Jamie Metzl: We have always fought against the inherent cruelty of natural selection, one of the two essential pillars of Darwinian evolution. We are now beginning to hack away at the second pillar, random mutation. Our growing understanding of how genes and biology function is opening the door to incredible medical applications like using genome sequencing and gene therapies to fight cancer and other diseases. But the healthcare applications of genetic technologies are only a station along the way to where these technologies are taking us.

Our ability to select embryos during in vitro fertilisation (IVF)—based on informed genetic predictions of both health-related traits and intimate characteristics like height, IQ and personality style—will grow over the coming years. We’ll use stem cell technologies to expand the number of eggs that prospective mothers can use in IVF and therefore the range of reproductive options for parents. We’ll deploy gene editing tools far more precise than today’s CRISPR systems to make heritable genetic changes to our future offspring. Over the coming decades, Darwin’s original concept of random mutation and natural selection will gradually give way to a process that is far more self-guided than anything Darwin could have imagined.

The Economist: Changing the nature of what it means to be human has huge consequences. What are the main ones?

Mr Metzl: We have internalised the idea that information technology is variable, which is why we expect each generation of our phones and computers to be better than the last. It’s harder for us to come to grips with the idea that our biology could be as variable as our IT, even though we understand intellectually that somehow we evolved from single cell organisms to complex humans over the past 3.8 billion years. Starting to see all of life, including our own, as increasingly manipulable will force us to think more deeply about what values will guide us as we begin altering biology more aggressively.

If we want to avoid dividing our species into genetic have and have-nots—a dangerous reduction in our diversity—or a genetic determinism that undermines our humanity, we’ll need to start living our values. But though we need to be mindful of the dangers, we must also keep in mind that these technologies have the potential to do tremendous good. Someday they might well help us avoid extinction level events like dangerous synthetic pathogens, a warmer climate, the fallout from a nuclear war or the eventual expiration of our sun.

The Economist: Do we have the ethical framework to handle this? If not, what might it look like if things go wrong?

Mr Metzl: We create beautiful art, philosophy and universal concepts like human rights but wipe out millions of each other in wars and genocides and still today invest massive amounts of our collective wealth in tools of mass murder. The “better angels of our nature” remain primary drivers in our development of genetic technologies, but the dark side of human nature could also be empowered through these same tools. We need a very strong ethical and cultural framework to increase the odds that we’ll use these technologies wisely, not least because access to them will be decentralised and democratised.

Although the positive possibilities far outweigh the negatives, it would be crazy to ignore the many ways things could go wrong. Like Icarus, we could fly too close to the sun and get burned if we hubristically assume we know more than we actually do. Our gene drives could crash ecosystems. We could use these tools to undermine our common identity as a species and social cohesion. The good news is that while the technologies are new, the values we’ll need to use them wisely are often old.

The Economist: What sort of regulations need to be in place to “enable” these technologies—and what rules should “constrain” them?

Mr Metzl: Genetic technologies touch the source code of what it means to be human and must be regulated. This job is all the more difficult because the technology is racing forward faster than the governance structures around them can keep up. On both the national and international levels, we’ll need enough governance and regulation to prevent abuses and promote public safety while not so much to impede beneficial research and applications.https://0240ee3ef6e6a04a485b96e137b5379f.safeframe.googlesyndication.com/safeframe/1-0-38/html/container.html

To avoid dangerous medical tourism, every country should have a national regulatory system in place that aligns with international best practices and the country’s own values and traditions. We also have to start developing global norms that can ultimately underpin flexible international standards and regulations. These systems must be guided by core values rather than inflexible rules because what may now seem unthinkable, like actively selecting and even editing our future offspring, will increasingly become normalised over time. We urgently need to start preparing for what is coming.

The Economist: This takes the issue of human liberty to a new level (people should be free to change themselves or offspring), as well as the potential for unbridgeable inequalities (not just of wealth or life outcomes, but of capabilities encoded in oneself and family). How must the idea of liberalism adapt to address this? What does the “liberal agenda” look like for the 21st century vis-à-vis “hacking Darwin”?

Mr Metzl: If and when it becomes possible for some parents to give their children enhanced IQs, lifespans and resistance to disease, we will have to ask what this means for everyone else. Some will see these parents as first-adopters paving the way for everyone else, like the first privileged people buying smartphones. Others will call them usurpers laying the foundation for dangerously divided societies.

Whatever the case, differences within and between societies, fuelled by competition, will drive adoption of these technologies and present societies with stark choices. Too few regulations could lead to a dangerous genetic engineering free-for-all and arms race. But trying to ban genetic manipulations would increasingly require the trappings of the most oppressive police states. Some liberal societies may choose to provide a basic level of access to assisted reproduction and genetic-engineering services to everyone, not least to save the expense of lifetime care for people who would otherwise be born with preventable genetic diseases.

Societies already struggling to define the balance between the parental and state interests in the context of abortion will have an even tougher time drawing this line for parent-driven assisted reproduction. But if we thought the debates over abortion and genetically modified crops were contentious, wait until the coming debate over genetically modified people arrives. If we don’t want this to tear us asunder, we must all come together in a public process to figure out the best ways forward.

* * *

The disgraceful history of eugenics

Excerpted from “Hacking Darwin: Genetic Engineering and the Future of Humanity” by Jamie Metzl (Sourcebooks, 2019)

The term eugenics combines the Greek roots for good and birth. Although coined in the nineteenth century, the concept of selective breeding and human population culling has a more ancient history. Infanticide was written into Roman law and practiced widely in the Roman Empire. “A father shall immediately put to death,” Table IV of the Twelve Tables of Roman Law stated, “a son who is a monster, or has a form different from that of the human race.” In ancient Sparta, city elders inspected newborns to ensure that any who seemed particularly sickly would not survive. The German tribes, pre-Islamic Arabs, and ancient Japanese, Chinese, and Indians all practiced infanticide in one form or another.

The 1859 publication of Darwin’s The Origins of Species didn’t just get scientists thinking about how finches evolved in the Galapagos but about how human societies evolved more generally. Applying Darwin’s principles of natural selection to human societies, Darwin’s cousin and scientific polymath Sir Francis Galton theorized that human evolution would regress if societies prevented their weakest members from being selected out. In his influential books Hereditary Talent and Character (1885) and then Hereditary Genius (1889), he outlined how eugenics could be applied positively by encouraging the most capable people to reproduce with each other and negatively by discouraging people with what he considered disadvantageous traits from passing on their genes. These theories were embraced by mainstream scientific communities and championed by luminaries like Alexander Graham Bell, John Maynard Keynes, Woodrow Wilson, and Winston Churchill.

Although his work was partly in the spirit of the Victorian England times, Galton was then and even more now what we would call a racist. “The science of improving stock,” he wrote, “takes cognizance of all the influences that tend in however remote degree to give the more suitable races or strains of blood a better chance of prevailing speedily over the less suitable than they otherwise would have had.” In 1909, Galton and his colleagues established the journal Eugenics Review, which argued in its first edition that nations should compete with each other in “race-betterment” and that the number of people in with “pre-natal conditions” in hospitals and asylums should be “reduced to a minimum” through sterilization and selective breeding.

Galton’s theories gained increasing prominence internationally, particularly in the New World. Although eugenics would later accrue sinister connotations, many of the early adopters of eugenic theories were American progressives who believed science could be used to guide social policies and create a better society for all. “We can intelligently mold and guide the evolution in which we take part,” progressive theologian Walter Rauschenbusch wrote. “God,” Johns Hopkins economic professor Richard Ely asserted, “works through the state.” Many American progressives embraced eugenics as a way of making society better by preventing those considered “unfit” and “defective” from being born. “We know enough about eugenics so that if that knowledge were applied, the defective classes would disappear within a decade,” University of Wisconsin president Charles Van Hise opined.

In the United States, the “science” of eugenics became intertwined with disturbing ideas about race. Speaking to the 1923 Second International Congress of Eugenics, President Henry Osborn of New York’s American Museum of Natural History argued that scientists should:

“ascertain through observation and experiment what each race is best fitted to accomplish… If the Negro fails in government, he may become a fine agriculturist or a fine mechanic… The right of the state to safeguard the character and integrity of the race or races on which its future depends is, to my mind, as incontestable as the right of the state to safeguard the health and morals of its peoples. As science has enlightened government in the prevention and spread of disease, it must also enlighten government in the prevention of the spread and multiplication of worthless members of society, the spread of feeblemindedness, of idiocy, and of all moral and intellectual as well as physical diseases”.

Major research institutes like Cold Spring Harbor, funded by the likes of the Rockefeller Foundation, the Carnegie Institution of Washington, and the Kellogg Race Betterment Foundation, provided a scientific underpinning for a progressive eugenics movement growing in popularity as a genetic determinism swept the country. The American Association for the Advancement of Science put its full weight behind the eugenics movement through its trend-setting publication, Science. If Mendel showed there were genes for specific traits, the thinking went, it was only a matter of time before the gene dictating every significant human trait would be found. Ideas like these moved quickly into state policies.

Indiana in 1907 became the first U.S. state to pass a eugenics law making sterilization mandatory for certain types of people in state custody. Thirty different states and Puerto Rico soon followed with laws of their own. In the first half of the twentieth century, approximately sixty thousand Americans, mostly patients in mental institutions and criminals, were sterilized without their acquiescence. Roughly a third of all Puerto Rican women were sterilized after providing only the flimsiest consent. These laws were not entirely uncontroversial, and many were challenged in courts. But the U.S. Supreme Court ruled in its now infamous 1927 Buck v. Bell decision, that eugenics laws were constitutional. “Three generations of imbeciles,” progressive Supreme Court justice Oliver Wendell Holmes disgracefully wrote in the decision, “are enough.”

As the eugenics movement played out in the United States, another group of Europeans was watching closely. Nazism was, in many ways, a perverted heir of Darwinism. German scientists and doctors embraced Galton’s eugenic theories from the beginning. In 1905, the Society for Racial Hygiene was established in Berlin with the express goal of promoting Nordic racial “purity” through sterilization and selective breeding. An Institute for Hereditary Biology and Racial Hygiene was soon opened in Frankfurt by a leading German eugenicist, Otmar Freiherr von Verschuer.

Eugenic theories and U.S. efforts to implement them through state action were also very much on Adolf Hitler’s mind as he wrote his ominous 1925 manifesto, Mein Kampf, in Landsberg prison. “The stronger must dominate and not mate with the weaker,” he wrote:

“Only the born weakling can look upon this principle as cruel, and if he does so it is merely because he is of a feebler nature and narrower mind; for if such a law did not direct the process of evolution then the higher development of organic life would not be conceivable at all… Since the inferior always outnumber the superior, the former would always increase more rapidly if they possessed the same capacities for survival and for the procreation of their kind; and the final consequence would be that the best in quality would be forced to recede into the background. Therefore a corrective measure in favor of the better quality must intervene…for here a new and rigorous selection takes place, according to strength and health”.

One of the first laws passed by the Nazis after taking power in 1933 was the Law for the Prevention of Hereditary Defective Offspring, with language based partly on the eugenic sterilization law of California. Genetic health courts were established across Nazi Germany in which two doctors and a lawyer helped determine each case of who should be sterilized.

Over the next four years, the Nazis forcibly sterilized an estimated four hundred thousand Germans. But simply sterilizing those with disabilities was not enough for the Nazis to realize their eugenic dreams. In 1939, they launched a secret operation to kill disabled newborns and children under the age of three. This program was then quickly expanded to include older children and then adults with disabilities considered to have lebensunwertes leben, or lives unworthy of life.

Making clear the conceptual origins of these actions lay in scientifically and medically legitimated eugenics, medical professionals oversaw the murder of an ever-widening group of undesirables in “gassing installations” around the country. This model then expanded from euthanizing the disabled and people with psychiatric conditions to criminals and to those considered to be racial inferiors, including Jews and Roma, as well as homosexuals. It was not by accident that Joseph Mengele, the doctor who decided who would be sent to the gas chambers at Auschwitz, was a former star student of von Verschuer at the Frankfurt Institute for Hereditary Biology and Racial Hygiene.

By the mid-1930s, the American scientific community was pulling away from eugenics. In 1935, the Carnegie Institution concluded the science of eugenics was not valid and withdrew its funding for the Eugenics Records Office at Cold Spring Harbor. Reports of Nazi atrocities amplified by the 1945–46 Nuremberg trials put the nail in the coffin of the eugenics movement in the West. Although eugenics laws were finally scrapped from the books only in the 1960s in the United States and the 1970s in Canada and Sweden, very few people were forcibly sterilized after the war.

But as new technologies more recently began to revolutionize the human reproduction process and create new tools for assessing, selecting, or genetically engineering preimplanted embryos, many critics raised the specter of eugenics.

[…]

The parallels between the ugly eugenics of the late nineteenth century and the first half of the twentieth and what’s beginning to happen today are not insignificant. In both cases, a science at an early stage of development and with sometimes uncertain accuracy was or is being used to make big decisions—forced sterilization of the “feeble-minded” in the old days, not selecting a given embryo for implantation or terminating a pregnancy based on genetic indications today. In both cases, scientists and government officials seek to balance individual reproductive liberty with broader societal goals. In both cases, future potential children lose the opportunity to be born. In both cases, societies and individuals make culturally biased but irrevocable decisions about which lives are worth living and which are not. These parallels offer us a powerful warning.

But if we collectively paint all human genetic engineering with the brush of Nazi eugenics, we could kill the incredible potential of genetics technologies to help us live healthier lives. […] That there probably is an element of eugenics in decisions being made today on the future of human genetic engineering should push us to be careful and driven by positive values, but the specter of past abuses should not be a death sentence for this potentially life-affirming technology or the people it could help.

[…]

It’s not that hard to imagine future scenarios when humans would need to genetically alter ourselves in order to survive a rapid change in our environment resulting from global warming or intense cooling following a nuclear war or asteroid strike, a runaway deadly virus, or some kind of other future challenge we can’t today predict. Genetic engineering, in other words, could easily shift from being a health or lifestyle choice to becoming an imperative for survival. Preparing responsibly for these potential future dangers may well require we begin developing the underlying technologies today, while we still have time.

Thinking about genetic choice in the context of imagined future scenarios is, in many ways, abstract. But potentially helping a child live a healthier, longer life is anything but. Every time a person dies, a lifetime of knowledge and relationships dissolves. We live on in the hearts of our loved ones, the books we write, and the plastic bags we’ve thrown away, but what would it mean if people lived a few extra healthy years because they were genetically selected or engineered to make that possible? How many more inventions could be invented, poems written, ideas shared, and life lessons passed on? What would we as individuals and as a society be willing to pay, what values might we be willing to compromise, to make that possible? What risks would we individually and collectively be willing to take on? Our answers to these questions will both propel us forward and present us with some monumental ethical challenges.

Conclusion

The question should be what would you do to ensure that your children were healthy when they were born and would lead a long and healthy life? I sure most parents would lay down their lives for their children. Then why is it insane for parents wanting to eliminate preventable birth defects and genetic anomalies? While I don’t have any children of my own and nor will I have any. I made a conscious decision years ago that this was probably the biggest gift I could give the world, would be to have 1 to 2 less mouths to feed. Our planet is definitely over populated. Should we over burden it with individuals that will never be able to be productive members of society? This has been a question that has been answered in a variety of ways throughout our recorded history. Until the last 150 years, abortion and infanticide were accepted means of birth control and eliminating children with debilitating birth defects. As our planet becomes more and more over crowded, we need to address these issues.

Resources

yourgenome.org, “What is genetic engineering?;” academic.oup.com, “Human enhancement: Genetic engineering and evolution,” By Mara Almeida; nature.com, “Genetic Inequality: Human Genetic Engineering,” By: Danielle Simmons, Ph.D; future-science.com, “Genetically modified humans: the X-Men of scientific research,” By Jenny Straiton; jbiomeds.com, “Human, Social, and Environmental Impacts of Human Genetic Engineering,” By Satyajit Patra*, Araromi Adewale Andrew; statnews.com, “Experts debate: Are we playing with fire when we edit human genes?,” By Patrick Skerrett; newsharvard.edu, “Perspectives on gene editing,” By Mary Todd Bergman; economist.com, “How genetic engineering will reshape humanity,” By K.N.C.;

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