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Evolution, Genetic Engineering, and Human Enhancement

• INTRODUCTION
• Published: 09 November 2012
• Volume 25 , pages 439–458, ( 2012 )

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• Russell Powell 1 ,
• Guy Kahane 2 &
• Julian Savulescu 2  

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There are many ways that biological theory can inform ethical discussions of genetic engineering and biomedical enhancement. In this essay, we highlight some of these potential contributions, and along the way provide a synthetic overview of the papers that comprise this special issue. We begin by comparing and contrasting genetic engineering with programs of selective breeding that led to the domestication of plants and animals, and we consider how genetic engineering differs from other contemporary biotechnologies such as embryo selection. We go on to consider the implications of genetic engineering for human nature, human evolution, and persistence of the human species. Finally, we question whether genetic interventions warrant the extraordinary ethical scrutiny they are often given, and we show how the misleading “genetic blueprint” metaphor has imposed a faulty structure on the enhancement debate. We conclude by considering the nature of biological development and the sobering limits it places on what genetic engineering can reasonably hope to achieve

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Powell, R., Kahane, G. & Savulescu, J. Evolution, Genetic Engineering, and Human Enhancement. Philos. Technol. 25 , 439–458 (2012). https://doi.org/10.1007/s13347-012-0091-6

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Human Enhancement

The scientific and ethical dimensions of striving for perfection.

H uman enhancement is at least as old as human civilization. People have been trying to enhance their physical and mental capabilities for thousands of years, sometimes successfully – and sometimes with inconclusive, comic and even tragic results.

Up to this point in history, however, most biomedical interventions, whether successful or not, have attempted to restore something perceived to be deficient, such as vision, hearing or mobility. Even when these interventions have tried to improve on nature – say with anabolic steroids to stimulate muscle growth or drugs such as Ritalin to sharpen focus ­– the results have tended to be relatively modest and incremental.

But thanks to recent scientific developments in areas such as biotechnology, information technology and nanotechnology, humanity may be on the cusp of an enhancement revolution. In the next two or three decades, people may have the option to change themselves and their children in ways that, up to now, have existed largely in the minds of science fiction writers and creators of comic book superheroes.

Both advocates for and opponents of human enhancement spin a number of possible scenarios. Some talk about what might be called “humanity plus” – people who are still recognizably human, but much smarter, stronger and healthier. Others speak of “post-humanity,” and predict that dramatic advances in genetic engineering and machine technology may ultimately allow people to become conscious machines – not recognizably human, at least on the outside.

This enhancement revolution, if and when it comes, may well be prompted by ongoing efforts to aid people with disabilities and heal the sick. Indeed, science is already making rapid progress in new restorative and therapeutic technologies that could, in theory, have implications for human enhancement.

It seems that each week or so, the headlines herald a new medical or scientific breakthrough. In the last few years, for instance, researchers have implanted artificial retinas to give blind patients partial sight . Other scientists successfully linked a paralyzed man’s brain to a computer chip , which helped restore partial movement of previously non-responsive limbs. Still others have created synthetic blood substitutes , which could soon be used in human patients.

One of the most important developments in recent years involves a new gene-splicing technique called “clustered regularly interspaced short palindromic repeats.” Known by its acronym, CRISPR , this new method greatly improves scientists’ ability to accurately and efficiently “edit” the human genome, in both embryos and adults.

To those who support human enhancement, many of whom call themselves transhumanists, technological breakthroughs like these are springboards not only to healing people but to changing and improving humanity. Up to this point, they say, humans have largely worked to control and shape their exterior environments because they were powerless to do more. But transhumanists predict that a convergence of new technologies will soon allow people to control and fundamentally change their bodies and minds. Instead of leaving a person’s physical well-being to the vagaries of nature, supporters of these technologies contend, science will allow us to take control of our species’ development, making ourselves and future generations stronger, smarter, healthier and happier.

The science that underpins transhumanist hopes is impressive, but there is no guarantee that researchers will create the means to make super-smart or super-strong people. Questions remain about the feasibility of radically changing human physiology, in part because scientists do not yet completely understand our bodies and minds. For instance, researchers still do not fully comprehend how people age or fully understand the source of human consciousness.

There also is significant philosophical, ethical and religious opposition to transhumanism. Many thinkers from different disciplines and faith traditions worry that radical changes will lead to people who are no longer either physically or psychologically human.

Even minor enhancements, critics say, may end up doing more harm than good. For instance, they contend, those with enhancements may lack empathy and compassion for those who have not chosen or cannot afford these new technologies. Indeed, they say, transhumanism could very well create an even wider gap between the haves and have-nots and lead to new kinds of exploitation or even slavery.

Given that the science is still at a somewhat early stage, there has been little public discussion about the possible impacts of human enhancement on a practical level. But a new survey by Pew Research Center suggests wariness in the U.S. public about these emerging technologies. For example, 68% of Americans say they would be “very” or “somewhat” worried about using gene editing on healthy babies to reduce the infants’ risk of serious diseases or medical conditions. And a majority of U.S. adults (66%) say they would “definitely” or “probably” not want to get a brain chip implant to improve their ability to process information.

And yet, perhaps ironically, enhancement continues to captivate the popular imagination. Many of the top-grossing films in recent years in the United States and around the world have centered on superheroes with extraordinary abilities, such as the X-Men, Captain America, Spiderman, the Incredible Hulk and Iron Man. Such films explore the promise and pitfalls of exceeding natural human limits.

HUMAN ENHANCEMENT IN POPULAR CULTURE

[flipcards images=”https://www.pewresearch.org/wp-content/uploads/sites/9/2016/07/PS_2016.07.26_Human-Enhancement-Essay_Daedalus-250px.jpg, https://www.pewresearch.org/wp-content/uploads/sites/9/2016/07/PS_2016.07.26_Human-Enhancement-Essay_Frankenstein-250px.jpg, https://www.pewresearch.org/wp-content/uploads/sites/9/2016/07/PS_2016.07.26_Human-Enhancement-Essay_Gattaca-250px.jpg, https://www.pewresearch.org/wp-content/uploads/sites/9/2016/07/PS_2016.07.26_Human-Enhancement-Essay_Cap-250px.jpg” backs=”In the Greek myth, Daedalus fashioned wax and feather wings so that he and son Icarus could fly. But Icarus fell to his death because he flew too close to the sun, melting the wax., In Mary Shelley’s “Frankenstein” a scientist creates a new man only to ultimately die while trying to destroy his creation., The film Gattaca takes place in a future where non-genetically enhanced humans are considered “invalid.”, In the movies and comics, Captain America is a genetically-enhanced superhuman created to fight in America’s wars.”]

Not only is enhancement unquestionably part of today’s cultural zeitgeist, questions about humanity’s quest to move beyond natural limits go back to our earliest myths and stories. The ancient Greeks told of Prometheus, who stole fire from the gods, and Daedalus, the skilled craftsman, who made wings for himself and his son, Icarus. In the opening chapters of Genesis, the Hebrew Bible depicts a successful incident of human enhancement, when Adam and Eve ate the fruit from the tree of the knowledge of good and evil because the Serpent told them it would make them “like God.”

Of course, while Adam and Eve gained a new awareness and self-understanding, their actions also led to their expulsion from paradise and entry into a much harder world full of pain, shame and toil. This theme – that hidden dangers may lurk in something ostensibly good – runs through many literary accounts of enhancement. In Mary Shelley’s “Frankenstein” (1818), for instance, a scientist creates a new man, only to eventually die while trying to destroy his creation.

Whether these fears surrounding human enhancement are real or unfounded is a question already being debated by ethicists, scientists, theologians and others. This report looks at that debate, particularly in light of the diverse religious traditions represented in the United States. First, though, the report explains some of the scientific developments that might form the basis of an enhancement revolution.

[chapter title=”Where does the science stand?” background_image=”16058″]

O n Feb. 25, 2014, President Barack Obama met with Army officials and engineers at the Pentagon to discuss plans to create a new super armor that would make soldiers much more dangerous and harder to kill. The president joked that “we’re building ‘Iron Man,’” but Obama’s jest contained more than a kernel of truth: The exoskeleton, called the Tactical Assault Light Operator Suit (TALOS), does look vaguely like the fictional Tony Stark’s famous Iron Man suit. The first prototypes already are being built, and if all goes as planned, American soldiers may soon be much stronger and largely impervious to bullets.

A little more than a year later and an ocean away, scientists with the United Kingdom’s National Health Service (NHS) announced that by 2017, they plan to begin giving human subjects synthetic or artificial blood . If the NHS moves ahead with its plans, it would be the first time people receive blood created in a lab. While the ultimate aim of the effort is to stem blood shortages, especially for rare blood types, the success of synthetic blood could lay the foundation for a blood substitute that could be engineered to carry more oxygen or better fight infections.

In April 2016, scientists from the Battelle Memorial Institute in Columbus, Ohio, revealed that they had implanted a chip in the brain of a quadriplegic man. The chip can send signals to a sleeve around the man’s arm, allowing him to pick up a glass of water, swipe a credit card and even play the video game Guitar Hero .

Roughly around the same time, Chinese researchers announced they had attempted to genetically alter 213 embryos to make them HIV resistant. Only four of the embryos were successfully changed and all were ultimately destroyed. Moreover, the scientists from the Guangzhou Medical University who did the work said its purpose was solely to test the feasibility of embryo gene editing, rather than to regularly begin altering embryos. Still, Robert Sparrow of Australia’s Monash University Centre for Human Bioethics said that while editing embryos to prevent HIV has an obvious therapeutic purpose, the experiment more broadly would lead to other things. “Its most plausible use, and most likely use, is the technology of human enhancement,” he said, according to the South China Morning Post .

As these examples show, many of the fantastic technologies that until recently were confined to science fiction have already arrived, at least in their early forms. “We are no longer living in a time when we can say we either want to enhance or we don’t,” says Nicholas Agar , a professor of ethics at Victoria University in Wellington, New Zealand, and author of the book “Humanity’s End: Why We Should Reject Radical Enhancement.” “We are already living in an age of enhancement.”

The road to TALOS, brain chips and synthetic blood has been a long one that has included many stops along the way. Many of these advances come from a convergence of more than one type of technology – from genetics and robotics to nanotechnology and information technology. These technologies are “intermingling and feeding on one another, and they are collectively creating a curve of change unlike anything we humans have ever seen,” journalist Joel Garreau writes in his book “ Radical Evolution : The Promise and Peril of Enhancing Our Minds, Our Bodies – and What It Means to Be Human.”

The combination of information technology and nanotechnology offers the prospect of machines that are, to quote the title of Robert Bryce’s recent book on innovation, “Smaller Faster Lighter Denser Cheaper.” And as some futurists such as Ray Kurzweil argue, these developments will occur at an accelerated rate as technologies build on each other. “An analysis of the history of technology shows that technological change is exponential, contrary to the common-sense ‘intuitive linear’ view,” writes Kurzweil , an American computer scientist and inventor whose work has led to the development of everything from checkout scanners at supermarkets to text-reading machines for the blind. “So we won’t experience 100 years of progress in the 21st century – it will be more like 20,000 years of progress (at today’s rate).”

[icon_headline headline=”GENETIC EDITING AND ENGINEERING” image=”16088″ align=”aligntop”]

In the field of biotechnology, a big milestone occurred in 1953, when American biologist James Watson and British physicist Francis Crick discovered the molecular structure of DNA – the famed double helix – that is the genetic blueprint for life. Almost 50 years later, in 2003, two international teams of researchers led by American biologists Francis Collins and Craig Venter succeeded in decoding and reading that blueprint by identifying all of the chemical base pairs that make up human DNA.

Finding the blueprint for life, and successfully decoding and reading it, has given researchers an opportunity to alter human physiology at its most fundamental level. Manipulating this genetic code – a process known as genetic engineering – could allow scientists to produce people with stronger muscles, harder bones and faster brains. Theoretically, it also could create people with gills or webbed hands and feet or even wings – and, as Garreau points out in his book, could lead to “an even greater variety of breeds of humans than there is of dogs.”

In recent years, the prospect of advanced genetic engineering has become much more real, largely due to two developments. First, inexpensive and sophisticated gene mapping technology has given scientists an increasingly more sophisticated understanding of the human genome.

[than existing methods]

CRISPR is already dramatically expanding the realm of what is possible in the field of genetic engineering. Indeed, on June 21, 2016, the U.S. government announced that it had approved the first human trials using CRISPR, in this case to strengthen the cancer-fighting properties of the immune systems of patients suffering from melanoma and other deadly cancers. “CRISPR’s power and versatility have opened up new and wide-ranging possibilities across biology and medicine,” says Jennifer Doudna , a researcher at the University of California at Berkeley and a co-inventor of CRISPR.

According to Doudna and others, CRISPR could provide new treatments or even cures to some of today’s most feared diseases – not only cancer, but Alzheimer’s disease, Parkinson’s disease and others.

Jennifer Doudna, UC Berkeley

CRISPR’s power and versatility has opened up new and wide-ranging possibilities across biology and medicine.

[/pullquote]

An even more intriguing possibility involves making genetic changes at the embryonic stage, also known as germline editing. The logic is simple: alter the gene lines in an embryo’s eight or 16 cell stage (to, say, eliminate the gene for Tay-Sachs disease) and that change will occur in each of the resulting person’s trillions of cells – not to mention in the cells of their descendants. When combined with researchers’ growing understanding of the genetic links to various diseases, CRISPR could conceivably help eliminate a host of maladies in people before they are born.

But many of the same scientists who have hailed CRISPR’s promise, including Doudna, also have warned of its potential dangers. At a National Academy of Sciences conference in Washington, D.C., in December 2015, she and about 500 researchers, ethicists and others urged the scientific community to hold off editing embryos for now, arguing that we do not yet know enough to safely make changes that can be passed down to future generations.

Those at the conference also raised another concern: the idea of using the new technologies to edit embryos for non-therapeutic purposes. Under this scenario, parents could choose a variety of options for their unborn children, including everything from cosmetic traits, such as hair or eye color, to endowing their offspring with greater intellectual or athletic ability. Some transhumanists see a huge upside to making changes at the embryonic level. “This may be the area where serious enhancement first becomes possible, because it’s easier to do many things at the embryonic stage than in adults using traditional drugs or machine implants,” says Nick Bostrom, director of the Future of Humanity Institute , a think tank at Oxford University that focuses on “big picture questions about humanity and its prospects.”

But in the minds of many philosophers, theologians and others, the idea of “designer children” veers too close to eugenics – the 19th- and early 20th-century philosophical movement to breed better people. Eugenics ultimately inspired forced sterilization laws in a number of countries (including the U.S.) and then, most notoriously, helped provide some of the intellectual framework for Nazi Germany’s murder of millions in the name of promoting racial purity.

There also may be practical obstacles. Some worry that there could be unintended consequences, in part because our understanding of the genome, while growing, is not even close to complete. Writing in Time magazine , Venter, who helped lead the first successful effort to sequence the human genome, warns that “we have little or no knowledge of how (with a few exceptions) changing the genetic code will effect development and the subtlety associated with the tremendous array of human traits.” Venter adds: “Genes and proteins rarely have a single function in the genome and we know of many cases in experimental animals where changing a ‘known function’ of a gene results in developmental surprises.”

[icon_headline headline=”A BETTER BRAIN?” image=”16097″ align=”aligntop”]

For many transhumanists, expanding our capacities begins with the organ that most sets humans apart from other animals: the brain. Right now, cognitive enhancement largely involves drugs that were developed and are prescribed to treat certain brain-related conditions, such as Ritalin for attention deficit disorder or modafinil for narcolepsy. These and other medications have been shown in lab tests to help sharpen focus and improve memory.

But while modafinil and other drugs are now sometimes used (off label) to improve cognition, particularly among test-cramming students and overwhelmed office workers, the improvements in focus and memory are relatively modest. Moreover, many transhumanists and others predict that while new drugs (say, a specifically designed, IQ-boosting “smart pill”) or genetic engineering could result in substantially enhanced brain function, the straightest and shortest line to dramatically augmenting cognition probably involves computers and information technology.

As with biotechnology, information technology’s story is littered with important milestones and markers, such as the development of the transistor by three American scientists at Bell Labs in 1947. Transistors are the electronic signal switches that gave rise to modern computers. By shrinking the electronic components to microscopic size, researchers have been able to build ever smaller, more powerful and cheaper computers. As a result, today’s iPhone has more than 250,000 times more data storage capacity than the guidance computer installed on the Apollo 11 spacecraft that took astronauts to the moon.

One of the reasons the iPhone is so powerful and capable is that it uses nanotechnology, which involves “ the ability to see and to control individual atoms and molecules .” Nanotechnology has been used to create substances and materials found in thousands of products, including items much less complex than an iPhone, such as clothing and cosmetics.

Advances in computing and nanotechnology have already resulted in the creation of tiny computers that can interface with our brains. This development is not as far-fetched as it may sound, since both the brain and computers use electricity to operate and communicate. These early and primitive brain-machine interfaces have been used for therapeutic purposes, to help restore some mobility to those with paralysis (as in the example involving the quadriplegic man) and to give partial sight to people with certain kinds of blindness. In the future, scientists say, brain-machine interfaces will do everything from helping stroke victims regain speech and mobility to successfully bringing people out of deep comas.

Right now, most scientists working in the brain-machine-interface field say they are solely focused on healing, rather than enhancing. “I’ve talked to hundreds of people doing this research, and right now everyone is wedded to the medical stuff and won’t even talk about enhancement because they don’t want to lose their research grants,” says Daniel Faggella , a futurist who founded TechEmergence, a market research firm focusing on cognitive enhancement and the intersection of technology and psychology. But, Faggella says, the technology developed to ameliorate medical conditions will inevitably be put to other uses. “Once we have boots on the ground and the ameliorative stuff becomes more normal, people will then start to say: we can do more with this.”

Doing more inevitably will involve augmenting brain function, which has already begun in a relatively simple way. For instance, scientists have been using electrodes placed on the head to run a mild electrical current through the brain, a procedure known as transcranial direct-current stimulation (tDCS). Research shows that tDCS, which is painless, may increase brain plasticity, making it easier for neurons to fire. This, in turn, improves cognition, making it easier for test subjects to learn and retain things, from new languages to mathematics. Already there is talk of implanting a tDCS pacemaker-like device in the brain so recipients do not need to wear electrodes. A device inside someone’s head could also more accurately target the electrical current to those parts of the brain most responsive to tDCS.

Anders Sandberg, Oxford University’s Future of Humanity Institute

[Smart genes]

According to many futurists, tDCS is akin to an early steam train or maybe even a horse-drawn carriage before the coming of jumbo jets and rockets. If, as some scientists predict, full brain-machine interface comes to pass, people may soon have chips implanted in their brains, giving them direct access to digital information. This would be like having a smartphone in one’s head, with the ability to call up mountains of data instantly and without ever having to look at a computer screen.

The next step might be machines that augment various brain functions. Once scientists complete a detailed map of exactly what different parts of our brain do, they will theoretically be able to augment each function zone by placing tiny computers in these places. For example, machines may allow us to “process” information at exponentially faster speeds or to vividly remember everything or simply to see or hear better. Augments placed in our frontal lobe could, theoretically, make us more creative, give us more (or less) empathy or make us better at mathematics or languages. (For data on whether Americans say they would want to use potential technology that involved a brain-chip implant to improve cognitive abilities, see the accompanying survey, see U.S. Public Wary of Biomedical Technologies to ‘Enhance’ Human Abilities .)

Genetic engineering also offers promising possibilities, although there are possible obstacles as well. Scientists have already identified certain areas in human DNA that seem to control our cognitive functions. In theory, someone’s “smart genes” could be manipulated to work better, an idea that almost certainly has become more feasible with the recent development of CRISPR. “The potential here is really very great,” says Anders Sandberg, a neuroscientist and fellow at Oxford University’s Future of Humanity Institute. “I mean scientists are already working on … small biological robots made up of small particles of DNA that bind to certain things in the brain and change their chemical composition.

“This would allow us to do so many different things,” Sandberg adds. “The sky’s the limit.”

In spite of this optimism, some scientists maintain that it will probably be a long time before we can bioengineer a substantially smarter person. For one thing, it is unlikely there are just a few genes or even a few dozen genes that regulate intelligence. Indeed, intelligence may be dependent on the subtle dance of thousands of genes, which makes bioengineering a genius much harder.

Even if scientists find the right genes and “turn them on,” there is no guarantee that people will actually be smarter. In fact, some scientists speculate that trying to ramp up intelligence – whether by biology or machines – could overload the brain’s carrying capacity. According to Martin Dresler, an assistant professor of cognitive neuroscience at Radboud University in the Netherlands, some researchers believe that “evolution forced brains to develop toward optimal … functioning.” In other words, he says, “if there still was potential to optimize brain functioning by adding certain chemicals, nature would already have done this.” The same reasoning could also apply to machine enhancement, Dresler adds.

Even the optimistic Sandberg says that enhancing the brain could prove more difficult than some might imagine because changing biological systems can often have unforeseen impacts. “Biology is messy,” he says. “When you push in one direction, biology usually pushes back.”

[icon_headline headline=”THE FUTURE OF BLOOD” image=”16104″ align=”aligntop”]

Given the brain’s importance, cognitive enhancement might be the holy grail of transhumanism. But many futurists say enhancement technologies will likely be used to transform the whole body, not just one part of it.

This includes efforts to manufacture synthetic blood, which to this point have been focused on therapeutic goals. But as with CRISPR and gene editing, artificial blood could ultimately be used as part of a broader effort at human enhancement. It could be engineered to clot much faster than natural human blood, for instance, preventing people from bleeding to death. Or it could be designed to continuously monitor a person’s arteries and keep them free of plaque, thus preventing a heart attack.

Synthetic white blood cells also could potentially be programmed. Indeed, like virtually any computer, these cells could receive “software updates” that would allow them to fight a variety of threats, such as a new infection or a specific kind of cancer. 1

Scientists already are developing and testing nanoparticles that could enter the bloodstream and deliver medicine to targeted areas. These microscopic particles are a far cry from synthetic blood, since they would be used once and for very specific tasks – such as delivering small doses of chemotherapy directly to cancer cells. However, nanoparticles could be precursors to microscopic machines that could potentially do a variety of tasks for a much longer period of time, ultimately replacing our blood.

It’s also possible that enhanced blood will be genetically engineered rather than synthetically made. “One of the biggest advantages of this approach is that you would not have to worry about your body rejecting your new blood, because it will still come from you,” says Oxford University’s Sandberg.

Regardless of how it is made, one obvious role for enhanced or “smart” blood would be to increase the amount of oxygen our hemoglobin can carry. “In principle, the way our blood stores oxygen is very limited,” Sandberg says. “So we could dramatically enhance our physical selves if we could increase the carrying capacity of hemoglobin.”

According to Sandberg and others, substantially more oxygen in the blood could have many uses beyond the obvious benefits for athletes. For example, he says, “it might prevent you from having a heart attack, since the heart doesn’t need to work as hard, or it might be that you wouldn’t have to breathe for 45 minutes.” In general, Sandberg says, this super blood “might give you a lot more energy, which would be a kind of cognitive enhancement.”

(For data on whether Americans say they would want to use potential synthetic blood substitutes to improve their own physical abilities, see the accompanying survey, U.S. Public Wary of Biomedical Technologies to ‘Enhance’ Human Abilities .)

[icon_headline headline=”HYPE OR PARADIGM SHIFT?” image=”16105″ align=”aligntop”]

So where is all of this new and powerful technology taking humanity? The answer depends on who you ask.

Having more energy or even more intelligence or stamina is not the end point of the enhancement project, many transhumanists say. Some futurists, such as Kurzweil, talk about the use of machines not only to dramatically increase physical and cognitive abilities but to fundamentally change the trajectory of human life and experience . For instance, Kurzweil predicts that by the 2040s, the first people will upload their brains into the cloud, “living in various virtual worlds and even avoiding aging and evading death.”

Kurzweil – who has done more than anyone to popularize the idea that our conscious selves will soon be able to be “uploaded” – has been called everything from “freaky” to “a highly sophisticated crackpot.” But in addition to being one of the world’s most successful inventors, he has – if book sales and speaking engagements are any indication – built a sizable following for his ideas.

Kurzweil is not the only one who thinks we are on the cusp of an era when human beings will be able to direct their own evolution. “I believe that we’re now seeing the beginning of a paradigm shift in engineering, the sciences and the humanities,” says Natasha Vita-More, chairwoman of the board of directors of Humanity+, an organization that promotes “the ethical use of technology to expand human capacities.”

Still, even some transhumanists who admire Kurzweil’s work do not entirely share his belief that we will soon be living entirely virtual lives. “I don’t share Ray’s view that we will be disembodied,” says Vita-More, who along with her husband, philosopher Max More, helped found the transhumanist movement in the United States. “We will always have a body, even though that body will change.”

George Annas, Boston University

In the future, Vita-More predicts, our bodies will be radically changed by biological and machine-based enhancements, but our fundamental sensorial life – that part of us that touches, hears and sees the world – will remain intact. However, she also envisions something she calls a whole-body prosthetic, which, along with our uploaded consciousness, will act as a backup or copy of us in case we die. “This will be a way to ensure our personal survival if something happens to our bodies,” she says.

Others, like Boston University bioethicist George Annas, believe Kurzweil is wrong about technological development and say talk of exotic enhancement is largely hype. “Based on our past experience, we know that most of these things are unlikely to happen in the next 30 or 40 years,” Annas says.

He points to many confident predictions in the last 30 or 40 years that turned out to be unfounded. “In the 1970s, we thought that by now there would be millions of people with artificial hearts,” he says. Currently, only a small number of patients have artificial hearts and the devices are used as a temporary bridge , to keep patients alive until a human heart can be found for transplant.

More recently, Annas says, “people thought the Human Genome Project would quickly lead to personalized medicine, but it hasn’t.”

Faggella, the futurist who founded TechEmergence, sees a dramatically different future and thinks the real push will be about, in essence, expanding our consciousness, both literally and figuratively. The desire to be stronger and smarter, Faggella says, will quickly give way to a quest for a new kind of happiness and fulfillment. “In the last 200 years, technology has made us like gods … and yet people today are roughly as happy as they were before,” he says. “So, I believe that becoming a super-Einstein isn’t going to make us happier and … that ultimately we’ll use enhancement to fulfill our wants and desires rather than just make ourselves more powerful.”

What exactly does that mean? Faggella can’t say for sure, but he thinks that enhancement of the mind will ultimately allow people to have experiences that are quite simply impossible with our current brains. “We’ll probably start by taking a human version of nirvana and creating it in some sort of virtual reality,” he says, adding “eventually we’ll transition to realms of bliss that we can’t conceive of at this time because we’re incapable of conceiving it. Enhancing our brains will be about making us capable.”

[chapter title=”Ethics and religion” background_image=”16073″]

[icon_headline headline=”A TALE OF TWO HUXLEYS” image=”16100″ align=”aligntop”]

T o some degree, the ideas and concepts behind human enhancement can be traced to biologist and author Julian Huxley. In addition to being one of the most important scientific thinkers of the mid-20th century, Julian also was the brother of Aldous Huxley, author of the famous scientific dystopian novel “Brave New World . ”

The novel is set in a future where, thanks to science, virtually no one knows violence or want. But this brave new world also is a sterile place, where people rarely feel love, where children are “decanted” in laboratories and families no longer exist, and where happiness is chemically induced. Although there is an abundance of material comforts in this fictional world, the things that people traditionally believe best define our humanity and make life worth living – love, close relationships, joy – have largely been eliminated.

In contrast with his brother Aldous, Julian Huxley was a scientific optimist who believed that new technologies would offer people amazing opportunities for self-improvement and growth, including the ability to direct our evolution as a species. No longer, he said, would a person’s physical and psychological attributes be subject to the capricious whims of nature.

[icon_headline headline=”A COST TO SOCIETY?” image=”16101″ align=”aligntop”]

But like Julian’s brother Aldous Huxley, those who oppose radical enhancement say the road to transcending humanity is paved with terrible risks and dangers, and that a society that embraces enhancement might lose much more in the bargain than it gains. “I think that the enhancement imperative, where we’re going to overcome all limitations including death, seems to me to be a kind of utopianism that we’ll have to break a lot of eggs to realize,” says Christian Brugger, a professor of moral theology at St. John Vianney Theological Seminary in Denver.

According to Brugger and other opponents of radical enhancement, those “broken eggs” might include increased social tensions – or worse – as the rich and privileged gain access to expensive new enhancement treatments long before the middle class or poor and then use these advantages to widen an already wide gap between rich and poor. “The risks here of creating greater inequalities seem to be obvious,” says Todd Daly, an associate professor of theology and ethics at Urbana Theological Seminary in Champaign, Ill. “And I’m not convinced that people who get these enhancements will want to make sure everyone else eventually gets them too, because people usually want to leverage the advantages they have.”

For some thinkers, concerns about inequality go much further than merely widening the existing gap between rich and poor. They believe that radical enhancement will threaten the very social compact that underpins liberal democracies in the United States and elsewhere. “The political equality enshrined in the Declaration of Independence rests on the empirical fact of natural human equality,” writes social philosopher Francis Fukuyama in his 2002 book “Our Posthuman Future.” He adds: “We vary greatly as individuals and by culture, but we share a common humanity.”

Brugger of St. John Vianney Theological Seminary agrees. “Right now, there is a common equality because we are all human,” he says. “But all of this changes once we start giving some people significantly new powers.”

Supporters of human enhancement say the goal is not to create a race of superhumans but to use technological tools to improve humanity and the human condition. Indeed, they say, it is an extension of what humans have been doing for millennia: using technology to make life better. “I don’t believe in utopias and I don’t believe in perfection,” says Vita-More, adding that: “For me, enhancement is a very practical way to give us new options to make our lives better. It’s that simple.”

A good example, Vita-More says, is cognitive enhancement. “By giving people increased memory and problem-solving skills, cognitive enhancement will help us be more creative by giving us the ability to put more things together in new ways,” she says. “It will make us better problem solvers.”

James Hughes, Trinity College

The more ability we have as individuals, the better we become.

Those who support human enhancement also deny that these developments will make social inequalities dramatically worse. New technologies are often socially disruptive and can have a negative impact on certain vulnerable populations, they say. But the problem of inequality is essentially, and will remain, a political one.

“The core Luddite mistake is to point to a social problem and to say that if we add new technologies the problem will get worse,” says James Hughes, executive director of the Institute for Ethics and Emerging Technologies, a pro-enhancement think tank. “But the way to cure the problem in this case is to make the world more equal, rather than banning the technology.”

Human enhancement is just as likely, or even more likely, to mitigate social inequalities than to aggravate them, says Oxford University’s Bostrom, a leader in the transhumanist movement.  “The enhancement project could allow people who have natural inequalities to be brought up to everyone else’s level,” he says.

Hughes, Bostrom and others also dispute the idea put forth by Fukuyama and Brugger that enhancement could displace the sense of common humanity that has undergirded the democratic social contract for centuries. First, they point out that the history of the modern West has been one of an ever-expanding definition of full citizenship. “The set of individuals accorded full moral status by Western societies has actually increased, to include men without property or noble descent, women and non-white peoples,” Bostrom writes . In addition, supporters of enhancement say, the notion that there will be a distinctive species of enhanced individuals who will try to enslave their unenhanced brothers and sisters might make for good science fiction, but it is not likely to happen. Instead, they say, there will be many different types of people, with different types of enhancements. “It seems much more likely that there would be a continuum of differently modified or enhanced individuals, which would overlap with the continuum of as-yet-unenhanced humans,” Bostrom writes, adding that today there are very different types of people (very tall to very short, very intelligent to intellectually disabled, etc.) who manage to live side by side as moral and legal equals.

Finally, transhumanists and other supporters say, history shows that as people gain more control over their lives, they become more empathetic, not less. “Today we have more health, more intelligence and more lifespan than we did 100 years ago, and we’re more compassionate and more empathetic today then we were then,” Hughes says, pointing to a 2011 book by Harvard University psychology professor Steven Pinker, “The Better Angels of Our Nature: Why Violence Has Declined.” The book makes the case that as human society has grown richer and more sophisticated, it also has become less violent. “The more ability we have as individuals, the better we become,” Hughes adds.

[icon_headline headline=”A COST TO SELF?” image=”16102″ align=”aligntop”]

Christian Brugger, St. John Vianney Theological Seminary

Happiness is found in marriages, in families, in neighborhoods … None of these are promised by enhancement.

Critics of enhancement question whether people really will be happier if enhancement projects are allowed to come to fruition. According to these critics, philosophers have long held that true happiness does not come from enhanced physical prowess or dramatically longer life, but from good character and virtuous living. “Happiness is found in marriages, in families, in neighborhoods … in people who are willing to sacrifice and suffer for others,” Brugger says. “None of these are promised by enhancement.”

“Happiness also is found in limits, says Agar of Victoria University. “There are things that I value and am proud of in my life, like my recent book,” he says. “But how can I value the writing of my book if I’ve been cognitively enhanced, and doing such a thing becomes much easier?”

But supporters contend that life still will be meaningful and challenging in a world where enhancement is widespread. “The things that have to do with human character and virtue and those things that make life meaningful will not change as a result of human enhancement, just like they haven’t changed as our society has changed,” says Ted Peters, a professor of systematic theology at Pacific Lutheran Theological Seminary in Berkeley, California. “As long as we are still human, these things will be important.”

Furthermore, an enhanced life will still contain challenges and limits, just different ones, says Ronald Cole-Turner, a professor of theology and ethics at Pittsburgh Theological Seminary, which is associated with the Presbyterian Church (U.S.A.). “The challenges of life will still be there, they may just be different and harder,” he says. “The goal posts will have moved further down the field, that’s all.”

[icon_headline headline=”TRANSHUMANISM AND FAITH TRADITIONS” image=”16103″ align=”aligntop”]

Because human enhancement is still largely an issue for the future, it has not yet attracted a lot of attention in American religious communities. There is, for instance, no official teaching or statement on human enhancement or transhumanism that has come directly from any of the major churches or religious groups in the United States. However, some theologians, religious ethicists and religious leaders have started to think about the implications of human enhancement in light of their traditions’ teachings, offering a sense of how their churches or religions might respond to radical human enhancement if it became possible.

All of the Abrahamic faiths – Judaism, Christianity and Islam – share the belief that men and women have been created, to some extent, in God’s image. According to many theologians, the idea that human beings in certain ways mirror God make some, but not all, religious denominations within this broad set of connected traditions wary of using new technologies to enhance or change people, rather than heal or restore them.

The Roman Catholic Church, through its large network of educational and other institutions, already has begun formulating an argument against enhancement, based in part on the idea that God’s plan for humanity includes limits and that life’s limits are the very forces that create virtuous, wise and ultimately happy people. “Courage, fidelity, fortitude, generosity, hope, moderation, perseverance, are all cultivated in response to limitations of circumstance and nature,” says John Haldane, a Catholic philosopher who teaches at the University of St. Andrews in Scotland.

Todd Daly, Urbana Theological Seminary

…when we attempt to be something more than human, are we running the risk of trying to become, in some ways, like God, as did Adam and Eve?

Catholics actively support medical and technological advances that can restore someone to health, says Brugger. “But the dividing line for the church is the line between therapy and enhancement.”

Concerns about crossing that line already have been expressed by Catholic-affiliated organizations. In 2013, for instance, the church-affiliated International Science and Life Congress met in Madrid and issued a declaration that warned that “new human species, artificially manipulated” would create “a real danger to human life as we know it.”

[evangelical]

According to Daly and others, evangelicals’ opposition to enhancement would be based in part on the notion that man should not “play God.” According to Daly, “when we attempt to be something more than human, are we running the risk of trying to become, in some ways, like God, as did Adam and Eve?” He adds, “This is an important issue for Christians that, I think, will help drive the debate for us.”

John Haldane, University of St. Andrews

Courage, fidelity, fortitude, generosity, hope, moderation, perseverance, are all cultivated in response to limitations of circumstance and nature.

Opposition also would be likely from the Church of Jesus Christ of Latter-day Saints, which teaches that the body is sacred and thus must not be altered. While small enhancements that do not overtly change the body might be acceptable to Mormon leaders, more significant enhancements would probably be “seen as a problem by the church,” says Steven Peck, a bioethicist at Brigham Young University in Provo, Utah.

The Hindu tradition probably would approach human enhancement as a potentially dangerous development as well, although for different reasons than Christian churches, says Deepak Sarma, a professor of South Asian religions and philosophy at Case Western Reserve University in Cleveland. Enhancement is troubling, he says, because it could be used to alleviate suffering, which is necessary to work off bad karma (debt from bad deeds and intents committed during a person’s past lives). Viewed in this light, Sarma says, Hindus could see enhancement as keeping someone from cleansing themselves of these misdeeds from their past lives.

In Islam, according to Sherine Hamdy, an associate professor of anthropology at Brown University, human enhancement would be viewed with concern by some scholars and leaders and embraced by others. Supporters might see new enhancements as a way to help the Muslim world catch up with the West or “at least not get left further behind,” she says. Others would oppose enhancements out of a desire “not to change what God has created.”

According to Lutheran theologian Peters, many mainline churches will view enhancement positively because they will see aspects of it as attempts to improve human well-being and alleviate suffering. “I think they will see much of this for what it is: an effort to take advantage of these new technologies to help improve human life,” he says.

Hava Tirosh-Samuelson, Arizona State University

So long as the improvement alleviates or prevents suffering, it is inherently good …

Similarly, Buddhists would largely accept and even embrace human enhancement because it could help them become better Buddhists, says Hughes, who is an advocate for transhumanism as well as a Buddhist and a former Buddhist monk. Enhancement that extends life and makes people more intelligent “would be seen as good because you’d have more time to work on enlightenment and … you could be more effective in helping others,” he says.

[in Jewish law]

In spite of intense disagreements about the utility and morality of trying to “improve” humanity, many thinkers on both sides of the debate share the belief that if just some of the dreams of today’s transhumanists are realized, human society will change and change significantly. These changes, if they occur, will upend some social norms and possibly religious norms as well. And they will force churches and many other institutions (both religious and secular) to adjust to a new reality. For the first time in human history, the biggest material changes in our society may not be occurring outside of ourselves, in the fields, factories and universities that have shaped human civilization, but inside our bodies – in our brains and muscles and arteries, and even in our DNA.

• Kurzweil, Ray and Terry Grossman. 2004. “Fantastic Voyage: Live Long Enough to Live Forever,” Pp. 226-227. ↩

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Arguing For and Against Genetic Engineering

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Table of Contents

Harvard philosopher Michael Sandel recently spoke at Stanford on the subject of his new book, The Case against Perfection: Ethics in the Age of Genetic Engineering. He focused on the “ethical problems of using biomedical technologies to determine and choose from the genetic material of human embryos,” an issue that has inspired much debate.

Having followed Sandel’s writings on genetic enhancement for several years, I think that this issue deserves special thought. For many years, the specter of human genetic engineering has haunted conservatives and liberals alike. Generally, their main criticisms run thus:

First, genetic engineering limits children’s autonomy to shape their own destinies. Writer Dinesh D’Souza articulates this position in a 2001 National Review Online article: “If parents are able to remake a child’s genetic makeup, they are in a sense writing the genetic instructions that shape his entire life. If my parents give me blue eyes instead of brown eyes, if they make me tall instead of medium height, if they choose a passive over an aggressive personality, their choices will have a direct, lifelong effect on me.” In other words, genetic enhancement is immoral because it artificially molds people’s lives, often pointing their destinies in directions that they themselves would not freely choose. Therefore, it represents a fundamental violation of their rights as human beings.

Second, some fear that genetic engineering will lead to eugenics. In a 2006 column, writer Charles Colson laments: “British medical researchers recently announced plans to use cutting-edge science to eliminate a condition my family is familiar with: autism. Actually, they are not ‘curing’ autism or even making life better for autistic people. Their plan is to eliminate autism by eliminating autistic people. There is no in utero test for autism as there is for Down syndrome…[Prenatal] testing, combined with abortion-on-demand, has made people with Down syndrome an endangered population…This utilitarian view of life inevitably leads us exactly where the Nazis were creating a master race. Can’t we see it?” The logic behind this argument is that human genetic enhancement perpetuates discrimination against the disabled and the “genetically unfit,” and that this sort of discrimination is similar to the sort that inspired the eugenics of the Third Reich.

A third argument is that genetic engineering will lead to vast social inequalities. This idea is expressed in the 1997 cult film Gattaca, which portrays a society where the rich enjoy genetic enhancements—perfect eyesight, improved height, higher intelligence—that the poor cannot afford. Therefore, the main character Vincent, a man from a poor background who aspires to be an astronaut, finds it difficult to achieve his goal because he is short-sighted and has a “weak heart.” This discrepancy is exacerbated by the fact that his brother, who is genetically-engineered, enjoys perfect health and is better able to achieve his dreams. To many, Gattaca is a dystopia where vast gaps between the haves and have-nots will become intolerable, due to the existence of not just material, but also genetic inequalities.

The critics are right that a world with genetic engineering will contain inequalities. On the other hand, it is arguable that a world without genetic engineering, like this one, is even more unequal. In Gattaca, a genetically “fit” majority of people can aspire to be astronauts, but an unfortunate “unfit” minority cannot. In the real world, the situation is the other way round: the majority of people don’t have the genes to become astronauts, and only a small minority with perfect eyesight and perfect physical fitness—the Neil Armstrong types—would qualify.

The only difference is that in the real world, we try to be polite about the unpleasant realities of life by insisting that the Average Joe has, at least theoretically, a Rocky-esque chance of becoming an astronaut. In that sense, our covert discrimination is much more polite than the overt discrimination of the Gattaca variety. But it seems that our world, where genetic privilege exists naturally among a tiny minority, could conceivably be less equal (and less socially mobile) than a world with genetic engineering, where genetic enhancements would be potentially available to the majority of people, giving them a chance to create better futures for themselves. Supporters of human genetic engineering thus ask the fair question: Are natural genetic inequalities, doled out randomly and sometimes unfairly by nature, more just than engineered ones, which might be earned through good old fashioned American values like hard work, determination, and effort?

“But,” the critics ask, “wouldn’t genetic engineering lead us to eugenics?” The pro-genetic engineering crowd thinks not. They suggest that genetic engineering, if done on a purely decentralized basis by free individuals and couples, will not involve any form of coercion. Unlike the Nazi eugenics program of the 1930s, which involved the forced, widespread killing of “unfit” peoples and disabled babies, the de facto effect of genetic engineering is to cure disabilities, not kill the disabled. This is a key moral difference. As pointed out by biologist Robert Sinsheimer, genetic engineering would “permit in principle the conversion of all the ‘unfit’ to the highest genetic level.” Too often, women choose to abort babies because pre-natal testing shows that they have Down syndrome or some other ailment. If anything, genetic engineering should be welcomed by pro-life groups because by converting otherwise-disabled babies into normal, healthy ones, it would reduce the number of abortions.

In addition, the world of Gattaca, for all its faults, features a world that, far from being defined along Hitler-esque racial lines, has in fact transcended racism. Being blond-haired and blue-eyed loses its racially elitist undertones because such traits are easily available on the genetic supermarket. Hair color, skin color, and eye color become a subjective matter of choice, no more significant than the color of one’s clothes. If anything, genetic engineering will probably encourage, not discourage, racial harmony and diversity.

It is true that genetic engineering may limit children’s autonomy to shape their own destinies. But it is equally true that all people’s destinies are already limited by their natural genetic makeup, a makeup that they are born with and cannot change. A short person, for example, would be unlikely to join the basketball team because his height makes it difficult for him to compete with his tall peers. An ugly person would be unable to achieve her dream of becoming a famous actress because the lead roles are reserved for the beautiful. A myopic kid who wears glasses will find it difficult to become a pilot. A student with an IQ of 75 will be unlikely to get into Harvard however hard he tries. In some way or another, our destinies are limited by the genes we are born with.

In this sense, it is arguable that genetic engineering might help to level the playing field. Genetic engineering could give people greater innate capacity to fulfill their dreams and pursue their own happiness. Rather than allow peoples’ choices to be limited by their genetic makeup, why not give each person the capability of becoming whatever he or she wants to, and let his or her eventual success be determined by effort, willpower, and perseverance? America has long represented the idea that people can shape their own destinies. To paraphrase Dr. King, why not have a society where people are judged not by the genes they inherit, but by the content of their character?

Looking at both sides, the genetic engineering controversy does raise questions that should be answered, not shouted down. Like all major scientific advances, it probably has some negative effects, and steps must be taken to ameliorate these outcomes. For example, measures should also be taken to ensure that genetic engineering’s benefits are, at least to some extent, available to the poor. As ethicists Maxwell Mehlman and Jeffrey Botkin suggest in their book Access to the Genome: The Challenge to Equality, the rich could be taxed on genetic enhancements, and the revenue from these taxes could be used to help pay for the genetic enhancement of the poor. To some extent, this will help to ameliorate the unequal effects of genetic engineering, allowing its benefits to be more equitably distributed. In addition, caution must be taken in other areas, such as ensuring that the sanctity of human life is respected at all times. In this respect, pro-life groups like Focus on the Family can take a leading role in ensuring that scientific advances do not come at the expense of moral ethics.

At the same time, we should not allow our fear of change to prevent our society from exploring this promising new field of science, one that promises so many medical and social benefits. A strategy that defines itself against the core idea of scientific progress cannot succeed. Instead of attempting to bury our heads in the sand, we should seek to harness genetic engineering for its positive benefits, even as we take careful steps to ameliorate its potential downsides.

Stanford's Censorship: A Culture of Censorship

Stanford’s censorship: the end of the stanford internet observatory, stanford, what did you expect.

The rampage in Main Quad and the president’s office was as predictable as it is contemptible. By allowing disorder to fester, the University has earned its humiliation.

Stanford's Rigged Housing “Accommodations”

Aspects of the Genetic Enhancement Essay

• To find inspiration for your paper and overcome writer’s block
• As a source of information (ensure proper referencing)
• As a template for you assignment

Introduction

Genetic enhancement means using genetic editing technologies to introduce changes into the genome of the fetus to achieve improvements in the physical or mental health of the future child. This process raises bioethical debates: both scientists and the community still cannot come to a conclusion about whether genetic enhancement is morally justified. This paper will discuss this process in terms of standards of normalcy, children’s “right to an open future,” and the difference between biological and social concepts of health. I will argue that I would use genetic enhancement for my child and would make it permissible if I were a healthcare provider or a policymaker, even though it would reinforce negative societal attitudes toward disability.

If I could modify the fetus that would become my child, I would use this chance. So far, society has not evolved to the point where all people would have genuinely equal opportunities. Currently, standards of normalcy stipulate that normalcy is freedom from disability and physical and mental illnesses, although these attitudes can vary depending on the culture (Scull, 2022). Therefore, I would like my child to fit these standards because, this way, it will be easier for this child to live in this world. If I used this technology, I would find it morally acceptable to modify only health-related characteristics, such as the predisposition to serious illnesses, including Down syndrome and cancer. It would be morally unjustifiable to alter the child’s gender, eye color, and other health-related characteristics. As Scull (2022) notes, people often want to have children like themselves, which is why deaf people may want to have deaf children. I think that I am driven by the same logic when choosing to use genetic enhancement: since I do not have a physical or mental disability, I would like my child not to have it as well.

If I were a healthcare provider or a policymaker, I would feel slightly different. I would admit that some people want to leave the birth of their child to a chance, so I would not make genetic enhancement mandatory. Obliging individuals to genetically modify their children to prevent disability may strengthen negative societal attitudes toward disability (Scull, 2022). This is because there is a difference between the biological and social concepts of health. In biology, health is a lack of illness; in contrast, in sociology, health refers to individual and societal perceptions of health and illness. In other words, from a social perspective, individuals’ health focuses more on how society views individuals with a certain condition rather than on how these individuals feel. For example, even if an individual using a wheelchair can have a happy life, society may see this person as disabled and ill. In order to mitigate this societal disapproval of disability, policymakers should not make genetic enhancement mandatory.

There is another important aspect of genetic enhancement that I would need to address as a policymaker, namely, editing the genome to turn a healthy embryo into one with a disability. According to Scull (2022), this situation is morally distinct from leaving the birth of a child with a disability to a chance. The reason for this is that parents are morally prohibited from making their children worse off (Scull, 2022). Furthermore, the child’s “right to an open future” is involved in the issue of genetic enhancement. It is generally considered that children without disabilities have more life possibilities in the future. However, Scull (2022) argues that all people are constrained in some way, for example, by place, time, family, and other factors. Nevertheless, all other things being equal, people without disabilities have fewer opportunities than their counterparts without disabilities.

To sum up, attitudes toward genetic enhancement may vary depending on the social concept of health. If people view disability as a deviation from the standards of normalcy, they will prefer to use genetic enhancement to prevent disability in their children. As a healthcare provider or a policymaker, I would permit genetic enhancement to avoid disabilities but prohibit using it to add a disability to a healthy child.

Scully, J. L. (2022). Being disabled and contemplating disabled children. In J. M. Reynolds & C. Wieseler (Eds.), The disability bioethics reader (pp. 116-124). Routledge.

• Patenting of Genetic Information
• Hutchinson-Gilford Progeria Syndrome
• Gene Therapy and Genetic Enhancement
• Conceptualisation of Abnormality and Normality of People in Modern Society
• Deaf Studies and Deaf Education
• Neanderthal DNA in the Genomes
• Albinism: Causes, Symptoms, and Therapies
• Gene Therapies: The Market Access
• Discussion: Human Genome Sequencing
• Children's Temperament and Personality: Genetic Basis
• Chicago (A-D)
• Chicago (N-B)

IvyPanda. (2024, January 3). Aspects of the Genetic Enhancement. https://ivypanda.com/essays/aspects-of-the-genetic-enhancement/

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REVIEW article

Ethical challenges of germline genetic enhancement.

• 1 Department of Humanities, International University of Catalonia, Barcelona, Spain
• 2 Pharmacokinetics, Patient Care and Translational Bioethics Research Group, Catholic University of Murcia (UCAM), Murcia, Spain
• 3 Department of Pharmacy, Faculty of Health Sciences, Catholic University of Murcia (UCAM), Murcia, Spain

The new reproductive technologies have opened the door to different processes of germline genetic enhancement by which the characteristics of an individual according to the interests of the agents involved could be selected during its gestation. Although the initiative is apparently oriented towards developing individuals that would excel in society, critical voices raise the concerns about that this approach would generate and need for a reflection on the ethical, social and legal implications of these techniques and their implementation in society. We reviewed the literature about these issues throughout their historical records to date, focusing on the moral arguments and non-clinical aspects that affect the legal and social environment. We have observed various trends of thought with divergent positions (proactive, preventive, and regulatory) as well as a large number of articles that try to reconcile the different approaches. This review illustrates a series of concepts from the ethics and philosophy fields which are frequently used in studies that evaluate the ethical implications of germline genetic enhancement, such as dignity, benefit, autonomy, and identity. In addition, amongst the many unresolved controversies surrounding genetic enhancement, we identify procreative beneficence, genetic disassociation, gender selection, the value of disability, embryo chimerization, and the psychosocial inequality of potentially enhanced individuals as crucial. We also develop possible scenarios for future debate. We consider especially important the definition and specification of three aspects which are essential for the deployment of new reproductive technologies: the moral status of the embryo undergoing enhancement, the legal status of the enhanced individual, and the responsibility of the agents executing the enhancement. Finally, we propose the precautionary principle as a means to navigate ethical uncertainties.

Introduction

The interest for the physical, moral, or cognitive well-being of all human individuals and its transmission to following generations has existed in the minds of the wise and rulers for thousands of years. Accomplishing this objective demands to specify the means to reach it, something especially difficult when it comes to transmitting the biological features of parents to children, that is, the genetic inheritance. Throughout history, civilizations have implemented various means to achieve the correct transmission of biological inheritance, generally through negative laws that forbid the pairing of consanguineous individuals as well as incest ( Bittles, 2003 ). In these cases, the laws were not intended to “enhance” the inherited characteristics rather to avoid the emergence of diseases or inbred disabilities ( Güvercin and Arda, 2008 ), and the “worsening” of the offspring. However, in Plato’s Republic we may find the formulation of one of the first political theories trying to enhance the individuals of a society with proactive means. Amongst Plato’s proposals we may find the selection of couples, the controlled inbreeding and crossing, the classification of newborns and their upbringing, or abandonment according to their physiological characteristics ( Güvercin and Arda, 2008 ). The genetic enhancement proposal appeared again strongly at the end of the 19th century and for the first time its postulates were put together by Galton and triggered a series of measures in Western society that sought to improve the genetic inheritance, not only of the physiological characteristics of the population but also their intellectual and moral capacities. The means to achieve such improvement included marriage restrictions, selective sterilizations and control of immigration ( Galton, 1904 ). Later, after the Second World War, these approaches were stigmatized after the Nuremberg trials and became banned, although not in practice in several countries ( Tännsjö, 1998 ; Yap, 2007 ).

Thus, during the 80s of the last century, a second approach took place with a series of measures focused on preventing the spread of the disability–and disabled subjects–in society ( Hens et al., 2013 ; Thompson, 2017 ). These measures included prenatal diagnosis, favored by the approval of abortion laws. Shortly after, techniques for preimplantation genetic diagnosis and screening, thanks to the development of assisted reproduction techniques, were largely implemented. All this prompted a new legislation that was progressively adapted to new demands of society ( Fagot-Largeault, 1987 ). Simultaneously, dissenting voices appeared that criticized the commodification of human life, its conditioning and its designing ( Hirschman, 1991 ). Contrary, other authors emerged criticizing the alarmism and encouraging the development of suitable legislation to avoid abuses ( Resnik, 1994 ). Consequently, the role of independent, third party institutions become essential to evaluate the ethical dimension of the new techniques ( Pergament and Bonnicksen, 1994 ) and fostered new regulations based on empirical data and not on moral abstractions ( Bonnicksen, 1994 ). In this line, for example, the AMA Council on Ethical and Judicial Affairs put forward the criteria for accepting prenatal diagnosis and preimplantation genetic diagnosis, provided it was directed to therapeutic ends ( AMA, 1994 ; Agar, 1995 ; Nicholson et al., 1995 ). Even so, the preventive selection of embryos, the manufacture of experimental embryos and the accumulation of cryopreserved embryos, led to new debates. As the therapeutic purpose became more diffuse or gave way to enhancement interventions, the debates shifted towards aspects such as the identity, benefit and dignity of the new creatures ( Agar, 1995 ; Davis, 1995 ; Vines, 1995 ; Glannon, 1998 ).

A new phase was initiated in the 90s when novel cloning technology was developed and proposed for the acquisition or improvement of capabilities which are above the “normal” parameters for a human being ( Richter and Bacchetta, 1998 ; Scully and Rehmann-Sutter, 2001 ; Greely, 2004 ). This new approach was called “enhancement” and included the acquisition of physiological, genetic, cognitive, and moral capabilities ( Faust, 2008 ; Gordon-Solmon, 2015 ; DeGrazia, 2016 ). From the mid-1990s to the present, various initiatives have appeared trying to apply genetic enhancement to the individual for non-therapeutic purposes by means of manipulating, eliminating, or incorporating specific genes in adult subjects or in the germline ( Blackburn, 2004 ). What makes this new phase in quite distinctive is the implication that the intervened individual will survive, will transmit his/her genes and will become a subject of rights. The appearance of Dolly, a cloned sheep in 1997, would start this new period including social alarm before the unknown and reactions calling for legislative caution. In 1997, both American and European legislation proposed a ban on human cloning ( Newman, 2003 ; Hildt, 2016 ) which only had territorial influence. Despite these bans, there have been proposals for new therapies that take advantage of newer genetic technologies and which are loaded with controversy, such as human cloning involving nuclear transfer ( Robertson, 1998 ), mitochondrial replacement ( Rubenstein et al., 1995 ; Richter and Bacchetta, 1998 ), modification of the genomic map ( Agar, 1995 ; MacKay et al., 1997 ), and genetic edition CRISP/Cas9 ( Ishii, 2017a ; Ishii, 2017b ). Although the regulatory warnings seemed unanimous, the legislations were progressively adapted to the evolution of the different research evaluation committees. Therefore, there is a greater development of ethical objections and restrictions to research on severe medical conditions in some associations such as ESHG and ESHRE which remain more inclined to encourage social debate and to establish a moratorium ( De Wert et al., 2018 ). However, other associations such as ASHG and NASM tend to raise the social and political problems involved in conducting this research ( Lyon, 2017 ).

This new paradigm (“enhancement”) raises a recurrent question in the general health care field: what is the threshold between therapy and enhancement to intervene? Undoubtedly, the will to cure, intrinsic to the medical profession, is at its best in the effort to develop therapies targeting the cause of the problem, be it at the functional origin or at the structural level. In this context, gene therapy is a medical intervention which is considered proportionate in its intention and in its means — to recover lost health according to what it is to a human individual. On the contrary, genetic enhancement would try to modify non-pathological human traits and optimize capabilities in the individuals ( NHGRI, 2018 ). Without a doubt there exists an intrinsic desire for the human zenith, constructed on a theoretical conception of what a perfect human being ought to be. And it is precisely this vision that is currently being challenged and questioned: the very concept of human identity, paired with succeeding questions: is that identity immutable? Are there arguments for not modifying it? And how far can it be modified? ( Bostrom and Sandberg, 2009 ; Greenbaum, 2013 ; Macpherson and Segarra, 2017 ), and what are the long-term psychological and social consequences on individuals and populations ( GüellPelayo, 2014 ; Cabrera, 2017 ; Ishii, 2017b )? In fact, all these issues frame the ethical challenges of “genetic enhancement” and, specifically, the genetic enhancement applied to the individual’s germline, aimed to improve the capabilities of the human subject.

These interventions are becoming an incipient new field of bioethics where the ELSI perspective is essential at its core ( Henderson et al., 2012 ; Greenbaum, 2013 ; Macpherson and Segarra, 2017 ; Ishii, 2017a ; Ishii, 2017b ; De Melo-Martín, 2018 ; Tamir, 2018 ). This perspective permeates and affects all legislation of the clinical and pharmacology fields, subject to strict ethical controls, and associated to the precautionary principle ( Gonzalvo-Cirac et al., 2013 ). This principle is applied in other fields too, such as protection of the environment ( Rippe and Willemsen, 2018 ). In this context, a key question arises: is this sensitivity regarding the environment also present for genetic enhancement interventions in the individual’s germline? To answer this question, we carried out a literature review on the moral dimension of the problem and its non-clinical argumentation, that is, the argumentation generated in the process to assess the ethical dimensions to reject or support genetic enhancement carried out in the germline ( Sparrow, 2014b ; De Wert et al., 2018 ).

There is an on-going debate on germline genetic enhancement within the public media and amongst specialists ( Henderson et al., 2012 ) which manifests certain distrust towards solutions coming from the field of philosophy ( Hayry, 2003 ; Coggon, 2011 ; Selgelid, 2014 ). This leads scientific debates to commonly end up on discussions around the political and ideological spheres with trends which oscillate between the so-called bioconservatives versus bioliberals factions ( Roache and Savulescu, 2016 ). Both of them fluctuate between the anxiety before a new unpredictable technology and the demystification of their dangers ( Cartier-Lacave et al., 2016 ). Even so, there is no shortage of attempts to reconcile both tendencies and seek a third way ( Roduit et al., 2013 ; Shapshay, 2012 ; Qiu, 2016 ) that is able to integrate elements of both. For this reason, we have synthesized the reflections extracted from the various studies and grouped them into three main trends: preventive, proactive, and regulatory. It is worth noting that these tendencies show certain intertwining of their authors’ arguments and opinions but keeping their different starting points.

a. Preventive trend . This trend groups diverse currents of thought whose common element is the attempt to preserve the human nature from the initiatives of germinal line modification. The studies in this group contain reflections from the Christian tradition ( Polkinghorne, 2004 ; Massmann, 2018 ) and deontological philosophy ( Jensen, 2011 ; Kim, 2017 ). They caution about the risk of modifying the essential element of human corporality, the DNA. The most representative author is Habermas (2003) , who tries to analyze the reasons why we do not accept inherited nature and therefore would want to modify it genetically. It is an approach already evoked by other philosophers such as Kirkegard, Heidegger, or Jonas ( Malmqvist, 2007 ; Christiansen, 2009 ), but Habermas goes a step further and argues that genetic enhancement in germline is to use the human being which may end up ‘making use’ of his being. From Habermas’s perspective, the preservation of the “non-chosen” or inherited nature, would protect us from ourselves ( Neil, 2008 ), a protection that could be radically degraded if market laws were deployed in the reproductive industry ( Fox, 2008 ). These laws would eventually determine the criteria for any action facing enhancement, including genetic doping ( Gaffney and Parisotto, 2007 ; McKanna and Toriello, 2010 ), gene patents ( Rodriguez, 2016 ; Du, 2018 ; Greenbaum, 2011 ), or competition between enhanced beings ( Jensen, 2011 ). An additional critical approach may be added, fueled by the instability and insecurity of reprogenetic techniques leading to unpredictable consequences, in which case, use would be irresponsible ( Fox, 2010 ; GüellPelayo, 2014 ; Hildt, 2016 ; Newman, 2017 ; Fox, 2018 ). This would be particularly relevant regarding the modification of the germline by genetic editing techniques ( Niklas et al., 2015 ; Reagan, 2015 ; Sykora, 2015 ; Qiu, 2016 ). In summary, these studies may suggest that a balanced equation of risks and benefits would not suffice to determine the ethical assessment and morality of a technique. Rather, deeper understanding of key concepts identity, nature and dignity is necessary ( Chan, 2015 ; De Melo-Martín, 2018 ; Jensen, 2018 ).

b. Proactive trend . This trend rejects any intellectual barrier to research and claims to investigate freely, expanding knowledge, and eliminating alarmism ( Harris, 2015 ). Therefore, they propose to overcome the precautionary principle and dismiss the arguments of the slippery slope in order to avoid slowing down the development of science ( Pattinson, 2000 ; Bailey, 2001 ; Bernal, 2005 ). Thus, these authors propose cloning of germline DNA without any barriers ( Robertson, 1998 ); the non-therapeutic purposes of preimplantation genetic diagnosis to select the individual’s features ( Roberts, 2002 ; Sperling, 2011 ); the desire for greater intelligence by means of the selection of alleles ( Kirk, 2003 ); or the selection of children according to their human potential ( Gordon-Solmon, 2015 ), even if these initiatives were theoretical and utopian. It is common in these studies to denounce the impediments of moral restrictions ( Smith et al., 2012 ; Murphy, 2014 ) and the cautions against cloning and genetic editing ( Bernal, 2005 ; Fenton, 2006 ; Resnik and Vorhaus, 2006 ; Powell et al., 2012 ) although there is also moderate unwillingness to create hybrids between species ( Robert and Baylis, 2003 ; Savulescu, 2003 ). In general, any opposition from philosophical, religious or political origin to scientific progress is questioned ( Roberts, 2002 ; Brooke, 2004 ; Smolin, 2004 ) and a more empirical, less speculative analysis is pursued ( Chyrowicz, 2001 ; Blackburn, 2004 ; Selgelid, 2014 ). These studies transmit the perception that there are social needs which are imperative to meet urgently and any attempt to hinder ( obstaculizar ) this process may be considered an attack, not only to progress, but also to social and global welfare.

c. Regulatory trend . Another group of studies shows great sensitivity for the consequences, positive and negative, that may accompany genetic enhancement and try to solve it by proposing the need for clear legislation as a result of a public, open, and reflective debate ( Marden and Nelkin, 2000 ). This trend tries to be an in-between solution between the positions of the two previous trends ( Evitt et al., 2015 ; Thompson 2017 ). The regulatory trend anchors its main argument on the utilitarian pragmatism approach. Thus, it proposes decisions based on the function they may generate on the individual and in society. At the same time, this tendency considers essential to rely on strong laws to avoid abuses, keeping open to debate certain interventions, marked by individual or social need: e.g. cloning for sterile couples ( Strong, 1998 ), the elimination of defective embryos ( Verlinsky, 2005 ), the selection of embryos with antisocial genes ( Tabery, 2009 ), the gamete planning ( Delaney, 2011 ) or the experimentation with embryos without procreative purposes ( De Miguel Beriain, 2019 ). At the same time, supporters of this regulatory approach also show concern for the social implications ( Marden and Nelkin, 2000 ), especially injustice and inequality that could generate ( Shapiro, 2005 ; Sparrow, 2015 ). There is, therefore, a great sensitivity to understand the consequences ( Mehlman, 2003 , Mehlman, 2005 ; Delaney, 2011 ; Anomaly, 2018 ) and a special interest to ensure coherent, global and coordinated legislation ( Mackenzie, 2005 ; Ishii, 2014 ; Kaebnick, 2017 ; Kanaris, 2017 ; Lyon, 2017 ; Ishii, 2017a ; Ishii, 2017b ; Liao, 2019 ).

As indicated above, studies on genetic enhancement on the germline employ concepts which are used beyond the scientific–experimental dimensions of the problem and reach an ethical–logical dimension, more typical of philosophical approaches ( Shapiro, 2005 ). This review has allowed us to highlight four significant concepts that are embedded in all debates and discussions addressing genetic enhancement: benefit, autonomy, identity, and dignity. Moreover, its significance differs in the various trends ( Table 1 ) and a short-term consensus on its importance and relevance is not foreseen.

a. Benefit . This is the focus of the discussion which configures the basis of the enhancement and is determined by the good that is pursued. For this reason, it is frequently addressed in most studies. The concept has been linked to the difference between the concepts “therapy” and “enhancement” which could also be interpreted as antagonists between the actions to “recover capacities” and means to “add capabilities” ( Du, 2018 ; Thompson, 2017 ). Based on this divergence, a first reflection looks into the value of the arguments promoting genetic enhancement in germline ( Neil, 2008 ) if the questions of what and why to enhance are not solved beforehand ( Henrich, 2011 ). A second reflection comes out from the supposed benefit or harm caused through modification of the DNA, the genes or the human identity ( Ebbesen and Jensen, 2006 ; Fenton, 2010 ). Some authors consider that modifications of human nature are advantageous ( Powell et al., 2012 ), while others consider it detrimental to human beings, due to the potential corruption of the human genome ( Sykora, 2015 ). In any case, the term benefit seems to be the most used amongst the authors and the foundation to carry out improvement and enhancement interventions.

b. Autonomy . The subject’s autonomy is a condition present sine qua non in any human initiative and makes possible the subject’s informed consent. Thus, can reprogenetics cause detriment to individual autonomy? The answer seems very controversial ( Mameli, 2007 ; Murphy, 2014 ; Schenker, 1997 ) due to deficient criteria with a comprehensive ethical assessment ( Selgelid, 2014 ). However, since the implementation of embryo selection techniques by means of prenatal diagnosis and preimplantation genetic diagnosis, there is a perception that these interventions may alter the autonomy of manipulated individuals ( Malmqvist, 2007 ; Henrich, 2011 ). This is especially evident when genetic enhancement is pursued: First, there are two wills which merge, the will of those responsible for the enhancement (e.g. parents, guardians or institutions) and the will of the enhanced individual ( Tamir, 2018 ) which may not always coincide. Furthermore, a second dilemma is posed: the autonomy of parents who want to have a child may be deeply conditioned by the balance between their personal interests and the altruism of their action ( Gordon-Solmon, 2015 ; DeGrazia, 2016 ; Jensen, 2018 ).

c. Identity . In its classical conception, human identity is considered what characterizes the human individual. It is a concept that integrates the biological basis and the rational features of the human being. Often it is assimilated to the concept of Aristotelian nature, as described by Habermas (2003) . However, a new definition and conceptualization of the meaning of identity seeks to include new technologies of genetic transformation ( Shapiro, 2005 ) and other aspects such as autonomy, interpersonal relationships and longevity ( Glannon and Harris, 2002 ). Nowadays, the lack of clear meaning and definition of the term identity is causing confusion in the debate on mitochondrial replacement and nuclear transfer techniques, as well as the proper identity of embryoids and chimaeras ( Scott, 2017 ; De Miguel Beriain, 2019 ). In addition, the dilemmas of social identity of children generated in vitro including confused filiation which consequences have not yet been studied in depth ( Rose and Novas, 2005 ; Lock and Nguyen, 2010 ) are added to the above problems. It is generally assumed that the concept of identity will be decisive to guide reflections on the moral status of the embryo ( DeGrazia, 2012 ; Francis, 2015 ).

d. Dignity . It is the most discussed concept in the debate on germline genetic enhancement and it is strongly contextualized and linked to the concept of identity ( Savulescu, 2003 ). In spite of being used repeatedly, it is not well defined in the debate and it remains unclear ( Henrich, 2011 ). Originally, this concept was mostly discussed in the debate on cloning ( Caulfield, 2003 ), chimerization ( Robert and Baylis, 2003 ; De Melo-Martín, 2008 ), and cryopreserved embryos ( Glannon and Harris, 2002 ; Ehrich et al., 2010 ). Hence there have been repeated attempts to develop new conceptualizations rooted on neurological basis, consensual basis or rational basis ( Bostrom and Sandberg, 2009 ; Jotterand, 2010 ; Chan, 2015 ). Undoubtedly, Habermas is the author who develops most deeply this term, dignity (p.29) ( Habermas, 2003 ) in the field of genetics, especially due to its relationship with the concept of human nature. This concept would confer an infinite value to the fact of being human which would grow to be the foundation for an unconditional respect towards individuals and their human rights ( Habermas, 2003 ; Christiansen, 2009 ).

Table 1 Summary of trends from the description of the main concepts.

Current Controversies

Next, we deal with the main aspects that have caused greater controversy in scientific, technological, legal, or philosophical forums about the existence of a human genetic identity and the free initiative to modify that identity ( Mehlman, 2003 ). This framework does not include other types of human improvement that science puts forward–physiological, cognitive or moral improvement through external elements such as drugs, surgery, or somatic genes–even if the focus remains similar: the happiness and well-being of individuals ( Bostrom and Sandberg, 2009 ; Savulescu et al., 2011 ). The fundamental difference of these tendencies with genetic enhancement in germline lies in a concept previously mentioned: the autonomy of the individual. The recipients of the genetic enhancement have not chosen to be better, something that is required for any other pharmacological, neuronal, or surgical improvement, which usually includes free, informed consent. Therefore, we focus on specific areas in which genetic improvement affects the fundamental rights (including future identity, dignity, and good lifetime) of individuals which are especially vulnerable and without autonomy, such as embryos or a newborn ( Liao, 2019 ).

Procreative Beneficence

Faced with the technology available and the possibility of predictably beneficial enhancements, a question comes out unstoppably: should not the selection of genes be mandatory? Shouldn’t governments be allowed to promote or prevent certain genes upon citizens in a similar way as it is done with vaccination programs ( Kanaris, 2017 ; So et al., 2017 )? Anticipating these issues, Savulescu developed what would be called “the Principle of Procreative Beneficence” by which parents would be morally obliged to discard an embryo with potential criminal genes and at the same time choose the embryos that have the most favorable genes for himself and for society ( Savulescu, 2001 ; Savulescu et al., 2006 ). This issue was already an old controversy, which was raised even before the emergence of prenatal diagnostic techniques and preimplantation genetic diagnosis: the obligation of the principle of beneficence against the foreseeable diseases present in the embryo, e.g. Huntington disease, Asperger syndrome, Down syndrome, cancer, cystic fibrosis, and spina bifida amongst others ( Harris, 2006 ; Walsh, 2010 ; Bosslet, 2011 ), removing the procreative autonomy of the parents ( Faust, 2008 ; DeGrazia, 2016 ). This state-driven intervention approach to eliminate the supposed “antisocial” embryos has been strongly criticized ( Tabery, 2009 ; Bosslet, 2011 ) due to the fact that it would require a substantial drift in the defense of human rights: it would not differentiate between a desire for moral enhancement and a mandatory action to implement it ( Saunders, 2015 ). The root of this disruption may be found in the moral imperative–the moral good as obligation–and its mandatory application leading to morally designed individuals ( Holland, 2016 ). In the same line, psychological pressure on parents would be especially significant ( Bonte et al., 2014 ) to encourage them to choose the “best” embryo amongst several, that would be the most “valuable,” “intelligent” or “excellent,” a quantification attitude that would seem incoherent, or at least surprising, for parents with unconditional affection for any of their children ( Tonkens, 2011 ; Jensen, 2018 ). Therefore, some authors have taken another approach and are inclined to transform the obligation into suggestion, option or advice ( Jacobs, 2015 ; Carter, 2015 ; Francis, 2015 ; Sparrow, 2015 ; Kanaris, 2017 ; Liao, 2019 ).

The Value of the Disability

The principle of procreative beneficence raises a new question: who is entitled to decide what an advantage is ( Karpin, 2007 ; Macpherson and Segarra, 2017 )? It is not clear whether some enhancements are desirable per se or whether a disability is deprived of any value ( Nunes, 2006 ; Francis, 2015 ). According to the expressivist objection current, the elimination of disabilities would be a loss of human identity for those who suffer them ( Alper et al., 2002 ; Malek, 2010 ; Collins et al. 2016 ; Shakespeare et al., 2017 ). Within the same context, then, we consider how negative interventions should be assessed: the selection of features that we may consider detrimental for the future child, e.g. deafness or Asperger, may also present some kind of benefit ( Karpin, 2007 ; Walsh, 2010 ; Graber, 2017 ). Would there be an obligation to avoid them? At this point, some authors have raised the concept of the “asymmetry of the damage,” by which the benefit of living with a disability would not compensate the damage of having it ( Glannon and Harris, 2002 ; Sparrow, 2012 ; Francis, 2015 ). Furthermore, the anti-equality shadow appears simultaneously, either by genetic enhancement or by embryonic selection technologies, since their application effectively would impose social segregation between the enhanced individuals and the non-enhanced subjects, who would identify themselves with the disabled ( Cavaliere, 2018 ). It is here where the legal regulatory bodies need to deepen the knowledge and the consequences of their implementation since mandatory actions to eradicate disability could lead to the extermination of full groups ( Kanaris, 2017 ; Thompson, 2017 ; Ishii, 2017a ).

Gender Selection

Undoubtedly, sex selection for non-therapeutic reasons has already generated a multitude of controversies ( Arnold et al., 2002 ; Sperling, 2011 ; Winckler, 2002 ). Currently, a new debate is taking place regarding the advantage or disadvantage of sexual dimorphism ( Sparrow, 2010a ) focused on the supposed “normality” of the existence of two sexes and whether one should prevail over the other ( Kahane and Savulescu, 2010 ; Slatman et al., 2010 ; Sparrow, 2010b ; Sparrow, 2012 ). If that normality were to be questioned, would it be justifiable to eliminate sexual dimorphism and select the best female or male genes to design an asexual being ( Kahane and Savulescu, 2010 )? This proposal could even go as far as to suggest the mandatory choice of the female subject by the tutors or the reproductive leaders upon consideration and assumption that the most aggressive genes would come from the male individual, an extremely controversial trait ( Slatman et al., 2010 ; Sparrow, 2012 ; Casal, 2013 ). According to other authors, this debate is insubstantial in nature because sexual dimorphism has a neutral effect on human development ( Kahane and Savulescu, 2010 ) and the normality of each of the sexes is accepted ( Sparrow, 2012 ). In spite of everything, the appearance of ectogenetic technologies will possibly repeat the controversies generated when the embryo selection techniques were and currently are applied to sex selection ( Kendal, 2017 ).

Creation of Chimeras, Hybrids, and Embryoids

Their creation has always raised rejection. The recent change of social mindset has been preceded by their potential usefulness in research, primarily related to therapeutics ( Brickman and Serup, 2017 ). This approach was fueled when IVF surplus human embryos began to be used to produce stem cells, thus justifying the elimination of any restriction on embryonic experimentation ( Robert and Baylis, 2003 ; Savulescu, 2003 ; Ehrich et al., 2010 ; Volarevic et al., 2018 ; De Miguel Beriain, 2019 ). In spite of everything, the doubt and aversion have persisted due to the uncertainty of the moral status of the hybrid human–animal individual ( Streiffer, 2005 ; Kaebnick, 2017 ). Moreover, this uncertainty acquires special relevance when the human–animal interaction may affect the brain structure and functionality as well as the gametes ( Dolgin, 2016 ; Levine and Grabel, 2017 ). The current trends range from the elimination of any restriction due to lack of ethical reasons, to the concern for individual and societal consequences ( Palacios-González, 2015 ; Hyun, 2016 ; Rodriguez, 2016 ). We believe that the solution can only be developed departing from a clear conceptualization of their moral status, a term still not agreed upon for embryos and much less for chimeras ( Giacomini et al., 2007 ; De Melo-Martín, 2008 ; Eberl and Ballard, 2009 ; Chan, 2015 ; Munsie et al., 2017 ; Hübner, 2018 ).

Genetic Untying

The problem of genetic untying or the absence of any genetic linkage between the embryo and the parents surged with the requirement of anonymity of the donors of the gametes for in vitro fertilization and surrogate motherhood. Further speculation to this debate has been added when taking into account the dissociating effects of new technologies, such as the IVR technique ( in vitro iterated reproduction) where the gametes are generated directly from the embryos and mitochondrial replacement technologies that involves genetic material from three gametes ( Bredenoord et al., 2011 ). In this technique, the intervention is not carried out directly on the embryo but on its precursors, e.g. its gametes ( Delaney, 2011 ). In all these cases, the result is an embryo genetically disconnected from its progenitors either because the gametes used are generated in vitro ( Palacios-González et al., 2014 ), or they are derived from multiple gametes, or they have been generated by iterated reproduction ( Sparrow, 2014a ). The end result is a “genetic orphan,” an individual without living parents, since the most immediate ancestor would be deceased embryos ( Sparrow, 2014b ); a situation which cannot be assimilated to the natural generation of monozygotic twins ( Douglas, 2014 ). The concern caused by mitochondrial donations and transfer techniques is flagrant generating new legislative doubts about the conditions for its application ( Ishii, 2014 ; Harris, 2015 ), especially regarding anonymity ( Brandt, 2016 ). Thus, there is discussion on the emergency of a new idea within the human procreation context: the abolition of procreative filiation and the possibility of raising design individuals without kinship ( Palacios-González et al., 2014 ; Roache, 2016 ).

Psychosocial Inequality

The alteration of the social balance has always been a great concern for the agents involved in enhancement efforts ( Davis, 1997 ; Davis, 2009 ). This has been even more explicit if it could affect the future of the child ( Sparrow, 2016 ; Krutzinna, 2017 ). The lack of restrictions makes it possible to foresee the social drift that these technologies may cause ( Mehlman, 2005 ; Ishii, 2017b ) although some authors consider this caution for inequality disproportionate ( Fenton, 2010 ) and limit their scope to assess of damage that might be predicted after implementation of enhancement interventions ( Persson, 2012 ). Even so, the fear of a social disadvantage in unenhanced children is recurrent and considered immoral and unjustified due to its potential for discrimination ( Jensen, 2011 ), the possible unknown consequences in complex thinking and reasoning ( Rosoff, 2011 ) and other long term secondary effects ( Glick, 2011 ). In this sense, the alarm over the application of techniques that we do not understand completely or do not know how to control ( GüellPelayo, 2014 ), ranges from conditioning and alteration of the child’s future ( Bredenoord et al., 2014 ) to a series of enhancements that eventually may lead to social fragmentation and disintegration ( Sparrow, 2015 ). For the moment, the debate has crystallized in the production of legislation that continues to be diffuse or even contradictory ( De Souza, 2015 ; Kim, 2017 ; Tamir, 2018 ).

Future Developments

Germline genetic enhancement presents important challenges that should be progressively clarified, mainly to prevent reproductive technology from being hijacked by its own advances. We must bear in mind that the ultimate reason for these initiatives is a concept of elementary ethics: the common good and the happiness of individuals. In essence, this is the engine that activates actions that promote, limit or regulate genetic technologies progress. We understand that a thorough argumentation within the ELSI framework, including the reprogenetic arena ( NHGRI, 2018 ), would be a way to ensure a proper application and implementation of any genetic enhancement initiative, whether theoretical or practical. In view of the studies reviewed, this working framework would have an impact on three fundamental questions where the ethical implications of the new technologies are rooted:

a) The moral status of the embryo . The issue was initially raised when the technologies that affected the integrity of the embryo were implemented pushing the debate about its nature and identity ( Fox, 2010 ; DeGrazia, 2012 ). The discussion and social debate about the embryo’s moral status became especially relevant when it came to specific issues such as the fate of hundreds of thousands of cryopreserved embryos, their use for experimentation, the consensual arbitrary limitation 14 days for research and the patented embryos ( Ehrich et al., 2010 ; Cavaliere, 2017 ; Chan, 2017 ; Appleby and Bredenoord, 2018 ). In fact, the fragility of this status is what allows the manipulation of embryos through genetic editing, provided that they are subsequently eliminated and not used in the germline. ( De Miguel Beriain, 2019 ). More recently, research the creation of transformed clones, hybrids, chimeras, and embryoid bodies has added a greater uncertainty to a question that remains unclear. It is not known exactly what the entity of embryoids, organoids, or synthetic embryos may be ( Chan, 2017 ; Kaebnick, 2017 ; Munsie et al., 2017 ). Society is looking for answers to formulate the most elementary question: what is it? or who is it? The reflection on the most basic definition of the principle of non-contradiction, something cannot be both true and not true in the same way and at the same time, pushes the debate towards a binary solution. The possibility that there may even be allowed the slightest manipulation of embryo beings, predictably human, without a defined identity status and without any biological linkage with anyone, could lead to a profuse and disturbing legislation to coax their adult development, whether they be clones, chimeras, enhanced chimeras, or enhanced embryos ( Mason, 2017 ; Scott, 2017 ; De Melo-Martin, 2018 ). In this context, the framework of reflection goes beyond the purely scientific or technological sphere and invades the anthropological arena. Thus, the philosophical framework in it anthropological dimension would be the one qualified to define the ontology of beings whose status is, apparently, diffuse, as well as their moral, social and legal identity ( Eberl and Ballard, 2009 ; Qiu, 2016 ). We consider it essential to determine the ontological status of these beings because its clarification will serve as a starting point to determine the administration of their destiny, either as non-human, their use, their property, or as human being, their respect and their rights ( Polkinghorne, 2004 ; Streiffer, 2005 ).

b) The rights of the modified individual . The question of genetic enhancement on the germline would not imply special obstacles if it were not because it breaks into the most intimate sphere of human beings in two dimensions: first, the decisions that are made and implemented will be irreversible and second, the genetic characteristics are likely not to have been chosen by the individual itself but imposed on him/her, not by nature but by a particular will. This situation was, precisely, the scenario that was aimed to avoid: the imposition by “nature” on the individual of certain characteristics that he or she had not chosen but rather had to accept resignedly. Would we be falling again into an injustice? What should be done if the modified individual does not accept his modified status? It could be argued that it is a scenario similar to an individual conceived in a natural way, (e.g. through sexual intercourse) who would not accept his/her condition or a specific feature (e.g. height, intelligence or even an inherited pathology, etc). However, there is an essential difference between both scenarios. The natural inheritance cannot be imputed to anyone, a key element for legislative purposes since the individual is not responsible for it. However, modified inheritance is the result of the deliberate action of other individuals (e.g. parents or guardians) who decide how the child should be. Therefore, they are fully responsible for the action carried out in the child with legal responsibility ( Sundby et al., 2018 ). In fact, there is general consensus about the non-implementation on children interventions with serious risks which may be not properly balanced with the benefit received from it ( Delaney, 2011 ; Powell and Buchanan, 2011 ). It is worth noting that therapies applied to children, who cannot agree to an informed consent (e.g. vaccination, corrective surgeries, etc) are only ethically justified when the benefit is the survival or the integrity of the newborn or child. In addition, those therapies should always respect their identity and should not lead to the modification or selective destruction of other individuals ( Millum, 2014 ; Hendrix et al., 2016 ).

But the existence of enhanced genes in the newborn inflicts characteristics that make that individual unique to himself and others ( Shapiro, 2005 ). Here a set of questions come out: did he have the right not to be enhanced? Did he have the right to reject imposed selection or imposed genes, positive or negative, not by the laws of nature but by the will of his managers? Does he have the right to a biological filiationties ( Malmqvist, 2007 ; Karpin, 2007 ; De Melo-Martín, 2018 )? If these rights existed, they would generate a dilemma of difficult solution: the need for an informed consent to undergo the enhancement procedure and at the same time the right of refusal to be modified ( Rodriguez, 2016 ). Furthermore, it would be unclear how to resolve its true biological identity–the cause and reason for its origin–and its right to biological filiation, a question that has already led to the modification of legislation about the anonymity of the donor of the gametes. In brief, will the enhanced individual have the right to know his detailed origin? Or the purpose of the enhancement carried out in him ( Reagan, 2015 ; Sykora, 2015 )? The analysis of the right to be a genetically enhanced individual is still in its infancy because it has yet materialized. In fact, some authors speculate that this right would depend on external factors to the individual ( Tamir, 2018 ), an approach that may cause additional restlessness. Consequently, we consider it essential to exercise extreme caution in all interventions ( Holm, 2019 ), in order to generate a truly human technology ( Nordberg et al., 2018 ).

c) The ethical, social and legal responsibility of the enhancement agents . The technologies of germline genetic enhancement carried out on individuals raise additional questions regarding the ownership of the action: Who is accountable for the changes, positive or negative, executed in individuals ( Rodriguez, 2016 ; Du, 2018 )? There are a variety of agents that could be expected to be accountable: the parents, the tutors, the researchers, the corporations, or even the State ( Sparrow, 2016 ), that is, any agent interested in the realization of the enhancement ( Millum, 2014 ; Kanaris, 2017 ). This accountability seems similar to the responsibility that is acquired when a therapeutic process is applied, however the motive and objective of the intervention produces a key difference between one and the other. In the case of therapies, it is understood that the responsibility is universal because it responds to an intrinsic need of every human being: the ultimate goal of the intervention is the health improvement of the intervened individual ( Bonte et al., 2014 ). Meanwhile, in genetic enhancement interventions, these needs are exceeded: the enhancement pursues to satisfy the desire of some individuals who decide the type of enhancement without clarifying who will assume the consequences ( Thompson, 2017 ; Ishii, 2017a ; Anomaly, 2018 ). Although some entities (NHGRI, ASHG, and ESHG) have expanded their scope of studies and include risk assessment, we agree with the authors who consider that these measures are insufficient ( Mehlman, 2009 ). Given that germline genetic enhancement application occurs at the beginning of the living stages of the human being (embryos, newborns, or even children), it is especially important to assess the long-term psychological and social consequences, with the conviction that there are red lines that should not be crossed ( Mehlman, 2005 ; Mehlman, 2009 ; Greenbaum, 2013 ).

It is probable that the desire for specific human enhancement will become a reality and, consequently, some agents will implement the germline’s genetic enhancement in society. For this reason, we consider essential to create effective expert panels and committees with society’s feedback ( Kaebnick, 2017 ) that could elaborate global normative documents, rooted and established on universal ethical principles ( Ishii, 2014 ; Lyon, 2017 ; De Wert et al., 2018 ).

The information about the creation of enhanced twins in China ( Regalado, 2018 ) reinforces our conviction about the need to put forward the underlying reasons that support future legislation aimed at prohibiting or allowing enhancements. Otherwise, if the different reasons are circumstantial without a deep foundation, the laws will be ineffective.

We propose the precautionary principle as a means to navigate ethics’ uncertainties and as the point of departure to assess moral enhancement. Certainly, an abusive application of the precautionary principle would lead to its ineffectiveness. Conversely, that precautionary attitude may improve the objectives and the means regardless whether it is directed to protect the autonomy of adults, the global human welfare or the dignity of the individual. We think that these concepts may structure and configure any advance in germline genetic enhancement technologies.

Author contributions

IM and IS developed and conceptualized the initial idea and carried out the revision process; MVR, IM and IS contributed to the discussion and elaboration of the sections.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Keywords: genetic enhancement, human identity, genetic interventions, reprogenetic, human procreation, precautionary principle, ELSI

Citation: Macpherson I, Roqué MV and Segarra I (2019) Ethical Challenges of Germline Genetic Enhancement. Front. Genet. 10:767. doi: 10.3389/fgene.2019.00767

Received: 06 November 2018; Accepted: 19 July 2019; Published: 03 September 2019.

Reviewed by:

Copyright © 2019 Macpherson, Roqué and Segarra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Ignacio Macpherson, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Human Enhancement , edited by Julian Savulescu and Nick Bostrom.

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Greg Bognar, Human Enhancement , edited by Julian Savulescu and Nick Bostrom., Mind , Volume 121, Issue 481, January 2012, Pages 225–229, https://doi.org/10.1093/mind/fzs034

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It is sometimes said that just as the twentieth century was the century of physics, the twenty-first century is going to be the century of molecular biology, genetics, and biotechnology. If that is the case, Minerva’s Owl started its flight early: there is already a subfield within philosophy that tries to understand the philosophical implications of these disciplines and to ‘give instruction’ for the use of genetic means to improve or ‘enhance’ human beings. In the last few years, the philosophical literature on enhancement has grown exponentially. Human Enhancement is a collection of previously published and new essays from leading thinkers on this field. It is an excellent entry point for those who are new to its debates.

As the editors point out in the introduction, it is hard to establish the precise boundaries of the field. The debates on genetic enhancement draw on different disciplines and raise new questions for them in turn. Moreover, it is unclear what ways enhancement by genetic means is different, from the moral perspective, from ‘enhancement’ by more familiar means—things like literacy, coffee, or computers. In the absence of clear boundaries, the best that can be done is to proceed on a case-by-case basis.

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The ethics of genetic cognitive enhancement: gene editing or embryo selection.

1. Introduction

2. therapeutic and non-therapeutic uses of assisted reproductive technologies (art).

• Contraceptive pills
• IVF (in vitro fertilization)
• PGD (preimplantation genetic diagnosis)
• Egg-freezing (oocyte cryopreservation)
• CRISPR (clustered regularly interspaced short palindromic repeats)
• In vitro gametogenesis (IVG)
• Time-lapse analysis of embryos
• Genome-wide association studies (GWAS)
• Artificial intelligence (AI)

3. IVG and CRISPR as a Means of GCE

4. public attitudes towards gce.

“ In this work, I have adopted the method that is, I believe, most fitting if one wants to take one’s route analytically from common cognition [gemeinen Erkenntnisse] to the determination of its supreme principle and in turn synthetically from the examination of this principle and its sources back to common cognition, in which we find it used ” [ 66 ] (p. 13).

“ Moral expertise is not the exclusive preserve of moral philosophers; instead, it is a domain in which a multitude of thoughtful people outside the academy make important contributions. The arena in which moral debate occurs is, accordingly, not limited to the peer-reviewed journals. Instead moral debate also, and almost certainly more importantly, takes place in newspapers and on television; in novels and films: everywhere moral conflicts are dramatized and explored ” [ 17 ] (pp. 309–310).

“ The unequal inheritance of wealth is no more inherently unjust than the unequal inheritance of intelligence. It is true that the former is presumably more easily subject to social control; but the essential thing is that as far as possible inequalities founded on either should satisfy the difference principle ” [ 80 ] (p. 245).

5. Conclusions

Acknowledgments, conflicts of interest.

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de Araujo, M. The Ethics of Genetic Cognitive Enhancement: Gene Editing or Embryo Selection? Philosophies 2020 , 5 , 20. https://doi.org/10.3390/philosophies5030020

de Araujo M. The Ethics of Genetic Cognitive Enhancement: Gene Editing or Embryo Selection? Philosophies . 2020; 5(3):20. https://doi.org/10.3390/philosophies5030020

de Araujo, Marcelo. 2020. "The Ethics of Genetic Cognitive Enhancement: Gene Editing or Embryo Selection?" Philosophies 5, no. 3: 20. https://doi.org/10.3390/philosophies5030020

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The Future of Human Nature: Drawing the Line Between Genetic Enhancements and Genetic Therapy

In a Tortoiseshell : In this excerpt of her essay on genetic enhancement and therapy, Asher Joy exemplifies how to create a motivated thesis by engaging in a complex, scientific debate. Drawing on interdisciplinary sources, Asher adds her own contribution to the debate at hand by pointing out a particular issue with the discourse surrounding genetic modifications and discusses the implications of such an error.

Excerpt / Asher Joy

As the age of genetic engineering looms ahead, the future of humanity seems at stake. In 2018, Dr. He Jiankui shocked the world when he announced that he had created the first genetically modified human by altering a gene in the embryos of twins Lulu and Nana before implanting the embryos in the mother’s womb, with the goal of making the babies resistant to HIV infection (Kolata et al.). Particularly salient in the immediate condemnation of this announcement were scientists, such as Dr. Shoukhrat Mitalipov, who expressed outrage at Jiankui’s actions arguing that he “did not do anything medically necessary” because such genetic alterations do not constitute a “‘seriously unmet need,’” as there are other non-invasive ways of preventing HIV infection (qtd. in Kolata et al). Similar sentiment arises from public opinion, such as CNN editor Jack Guy, who fears Jiankui’s experiment sets the stage of genetic engineering for “non-therapeutic purposes” (Guy). The anxieties about using genetic engineering for the sake of genetic enhancements instead of therapeutic purposes align with the opinions of the President’s Council on Bioethics, professor George Annas, and Dr. Leon Kass, who consider genetic enhancement, or the “directed use of biotechnical power to alter…the ‘normal’ workings of the human body and psyche, to augment or improve their native capacities and performances” (Kass et al. 13), to be reprehensible because genetic modification to better human abilities threatens “fundamental features of human nature” (Kass 123) by intervening in the natural endowment of the human genome. This suggests that these critics understand human biology as immutable.

However, such disavowal of genetic enhancements on the basis that human biology is inviolable yet endorsement of genetic therapy on existing individuals, or “the use of biotechnical power to treat individuals with known disabilities, or impairments, in an attempt to restore them to a normal state of health and fitness” (Kass et al. 13), reveals a contradiction to their belief in an inviolable human biology. This contradiction suggests that disabled or impaired individuals do not yet meet an acceptable biological standard of human nature. Such a belief positions human nature as one that is a biocultural construct with the goal of maintaining a static, universal status quo in humanity — one that ignores that both the concepts of “humans” and “nature” are defined not just by biology but through social, cultural, and environmental factors, causing them to be dynamic rather than stable, immutable constructs. The anxieties about violating human nature through genetic enhancement, contrasted with the relative acceptance of genetic therapy, reveal a reliance on a prejudicial, biocultural construct of human nature — a social construct which demeans those with disabilities or impairments, suggesting that their eligibility for genetic therapy implies that their genetic endowment does not meet an acceptable standard of human nature. Rather, examination of both “human” and “nature” as dynamic entities, the product of cultural, environmental, and genetic factors, reveals that the construct of “human nature” is constantly expanding and so does not belong in the genetic engineering debate about the acceptability of “enhancement” or “therapy.”

Author Commentary / Asher Joy

This excerpt is from my research paper “The Future of Human Nature: Drawing the Line Between Genetic Enhancements and Genetic Therapy” written for my writing seminar, “The Posthuman.” In my essay, I explore arguments against genetic engineering on the basis that it is a violation of human nature. My thesis centers around the fact that arguments regarding “human nature” do not belong in the context of the ethics of genetic engineering. 

My research began laboriously, as I poured through numerous articles discussing rather blunt “yes” or “no” answers to the ethics of genetic engineering. Nevertheless, I found it interesting that I encountered so many arguments vehemently against the idea. However, rather than rehashing this theme, I wanted to play devil’s advocate. Using peer reviewed articles, I found that many arguments revolved around several shared sources that strongly opposed genetic engineering. Upon examining these specific sources, I realized that they all touted this word “human nature” as if it were something that needed to be defended against the wiles of mankind. I then narrowed my argument to examine exactly what was this human and his/her nature that seemed so invincible. 

At this point, I was still formulating a “yes” or “no” (although I was leaning toward the “yes”) of the ethics of genetic engineering. Through this mindset, I postulated: what if I do support genetic engineering, what will happen then? This move was rather difficult, considering I felt that my voice would not be acknowledged in comparison to such scholars. Nevertheless, using this logic, I suddenly realized that the sources I had been working with already supported some sort of genetic engineering — genetic therapy. However, in this case such therapy was not a violation of human nature. Using this new information as the crux of my argument, my writing seminar professor helped me transform my argument from a “yes” or “no” response to rather one that acknowledged that there was something much more complex involved in the argument that specifically used human nature as a reason to disavow genetic engineering. 

Through this move, along with countless revisions, I was able to formulate a thesis that relied not on a simple response, but rather one that required much more complicated logic and reasoning. The revision process was especially difficult, as I wanted to make sure that I was properly representing my sources and they themselves presented conflicting details as to their argument. I also wanted to acknowledge that they also admitted some of the arguments that I wanted to include to use against their logic. Nevertheless, I still held onto the central theme that they supported genetic engineering while also disavowing genetic therapy and moved on to finding sources that would further help me establish my own voice in the conversation.

Editor Commentary / Alex Charles

Entering into a scholarly debate with experts in an academic field can be uncomfortable, difficult, and complicated. The works of such experts are always sophisticated and tidy. It often takes hours of research simply to understand their intricate arguments. Moreover, it requires even more research and preparation to take a multitude of scholars and use their opinions as building blocks by which you can create a unique essay of your own and contribute to the field of existing work. In her essay, however, Asher Joy does exactly that in two cogent, succinct paragraphs. 

Asher explains an existing debate in the field of genetic enhancement and therapy and uses a third source, Donna Haraway, to expose and explain the flaws in the discourse surrounding genetic modifications. Consequently, Asher gives her essay a clear motive—the contribution which her paper makes to the work of geneticists. Asher does not merely summarize the opinions of different scientists, but rather she creates a new lens with an additional author, through which she is able to find a peculiarity in the debate at hand. 

In her author commentary, Asher acknowledges that at first, she was nervous that her opinion “would not be acknowledged in comparison to such scholars.” However, Asher was able to combat this fear through the tactical positioning of different scholars. This strategy is known in the Writing Center as a Gaipa move, and in this case, Asher uses a move called “crossbreeding with something new.” This positioning is predicated on the notion that the author reinterprets an existing conversation or debate by using new source material to establish an original framework. 

In her essay, Asher executes this complicated Gaipa move by first explaining the puzzle she found in her research—the apparent hypocrisy of scientists to condemn genetic enhancement but support genetic therapy. Brilliantly, Asher also delineates between her scholars, those who support gene enhancement and those who do not, thus creating the impression that more evidence is required in order to claim which side, if any, is correct in their argumentation. She then dives deeper into this incongruity surrounding human biology, using a new framework of human biology as “discourse” to arrive at the conclusion that the error of scholars is in their incorporation of the idea of “human nature.” Consequently, Asher is able to make a significant contribution—one supported by the use of an additional outside source—to a stagnated debate over bioethics.

Professor Commentary / Professor Marina Fedosik, Princeton Writing Program

Asher’s essay “ The Future of Human Nature: Drawing the Line Between Genetic Enhancements and Genetic Therapy” grew out of her interest in genetic engineering. To narrow her interest down to a feasible motive, she decided to look at a specific experiment that provoked a heated discussion both in popular culture and among regulatory bodies and scientists. Asher is using cultural studies approaches and is drawing on sources from different disciplines as she writes to understand the polarization of conversation about genetic engineering. She enters a scholarly conversation by challenging an assumption shared by two bioethicists and pointing out the reliance of their arguments on a slippery key term: “human nature.” Asher is establishing this layer of motive by naming a bias that warrants an intervention in the conversation: the scholars rely on the concept of “immutable biology” to justify resistance to genetic enhancement, yet simultaneously they conceive of biology as in need of remediation when approving of genetic therapy. This clearly named insufficiency opens up space for Asher’s own voice. She can now respond to other scholars by developing a complex idea of her own in order to address the limits of their thinking. 

Asher’s thesis has several conceptual layers. The overarching claim that critiques the political use of the term “human nature” is further complicated by an explanation of different ways we can conceive of biology. The essay draws on Donna Haraway’s understanding of biology as a discourse and explains why “human nature” is an inadequate term for a discussion of genetic engineering and therapy ethics. The thesis of this essay is a compelling outcome of analysis that contributes to an ongoing conversation by transcending the positions already established within it. Asher refines the established methodology and directs our attention towards a new direction in thinking about issues in genetic engineering.

Works Cited 

Guy, Jack. “’Designer Babies’ Could Be Just Two Years Away, Expert Claims.” CNN, Cable News Network, 19 Nov. 2019, www.cnn.com/2019/11/19/health/designer-baby-analysis-scli-intl-scn/index.html.

Kass, Leon. Life, Liberty, and the Defense of Dignity: The Challenge for Bioethics. San Francisco: Encounter Books, 2002.

Kass, Leon, et al. Beyond Therapy: Biotechnology and the Pursuit of Happiness. Washington, D.C.: The President’s Council on Bioethics, 2003.

Kolata, Gina, et al. “Chinese Scientist Claims to Use Crispr to Make First Genetically Edited Babies.” The New York Times, The New York Times, 26 Nov. 2018.

Asher Joy ’23 was born and raised in Greensburg, Pennsylvania. She plans to study economics and maybe get a certificate in finance. When she’s not studying, she enjoys working out, eating, and sleeping. She wrote this essay as a first-year. 

Alex Charles ’22 is a prospective Woodrow Wilson major who plans on pursuing a Statistics and Machine Learning certificate. On campus he enjoys working with students in the Writing Center, coaching in the Dillon Youth Basketball league, and competing on the University’s men’s soccer team. He wrote this as a sophomore.

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Human enhancement

Mara almeida.

1 Centro de Filosofia das Ciências da Universidade de Lisboa, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisbon, Portugal

2 Department of Anatomy, College Medicine, Howard University, 520 W St. NW, Numa Adams Building, Room 1101, Washington, DC 20059, USA

Genetic engineering opens new possibilities for biomedical enhancement requiring ethical, societal and practical considerations to evaluate its implications for human biology, human evolution and our natural environment. In this Commentary, we consider human enhancement, and in particular, we explore genetic enhancement in an evolutionary context. In summarizing key open questions, we highlight the importance of acknowledging multiple effects (pleiotropy) and complex epigenetic interactions among genotype, phenotype and ecology, and the need to consider the unit of impact not only to the human body but also to human populations and their natural environment (systems biology). We also propose that a practicable distinction between ‘therapy’ and ‘enhancement’ may need to be drawn and effectively implemented in future regulations. Overall, we suggest that it is essential for ethical, philosophical and policy discussions on human enhancement to consider the empirical evidence provided by evolutionary biology, developmental biology and other disciplines.

Lay Summary: This Commentary explores genetic enhancement in an evolutionary context. We highlight the multiple effects associated with germline heritable genetic intervention, the need to consider the unit of impact to human populations and their natural environment, and propose that a practicable distinction between ‘therapy’ and ‘enhancement’ is needed.

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 [ 1–3 ]. 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 [ 4 , 5 ]. In addition, synthetic blood substitutes have been created, which could be used in human patients in the future [ 6–8 ].

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 [ 9 ]. 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’ [ 10 ]. 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’ [ 11 ]. 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 [ 12 , 13 ]. 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 [ 14–16 ], that could allow us to live longer, healthier and even happier lives [ 17 ]. 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 [ 18 , 19 ].

There is an ongoing debate between transhumanists [ 20–22 ] and bioconservatives [ 18 , 19 , 23 ] on the ethical issues regarding the use of technologies in humans. The focus of this commentary is not centred 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 [ 26–28 ]. 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 [ 29 ].

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 [ 29 , 30 ]. 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 [ 31 ]. 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 [ 32 ]. 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 [ 33 ]. Some studies have also shown that defective CCR5 can have a positive effect in cognition to enhance learning and memory in mice [ 34 ]. 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 [ 35 ]. 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 [ 36 ]. 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 [ 37 ]. 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 [ 38 ]. 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 [ 17 ]. 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 [ 20–22 ]. 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 [ 39 ]. 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 [ 40 ].

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 analysing which genetic alterations have been eventually associated with specific changes within the recent evolutionary history of humans. On this front, a key study has analysed 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’ [ 41 ]. 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 [ 41 ]. 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 [ 42–44 ]. Given that, according to recent studies within the field of biological anthropology recent human evolution has been in fact a process of ‘self-domestication’ [ 45 ], 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.

This work was supported by Fundação para a Ciência e a Tecnologia (FCT) of Portugal [CFCUL/FIL/00678/2019 to M.A.].

Conflict of interest : None declared.

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• Published: 20 April 2022

Beyond safety: mapping the ethical debate on heritable genome editing interventions

• Mara Almeida   ORCID: orcid.org/0000-0002-0435-6296 1 &
• Robert Ranisch   ORCID: orcid.org/0000-0002-1676-1694 2 , 3  

Humanities and Social Sciences Communications volume  9 , Article number:  139 ( 2022 ) Cite this article

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Genetic engineering has provided humans the ability to transform organisms by direct manipulation of genomes within a broad range of applications including agriculture (e.g., GM crops), and the pharmaceutical industry (e.g., insulin production). Developments within the last 10 years have produced new tools for genome editing (e.g., CRISPR/Cas9) that can achieve much greater precision than previous forms of genetic engineering. Moreover, these tools could offer the potential for interventions on humans and for both clinical and non-clinical purposes, resulting in a broad scope of applicability. However, their promising abilities and potential uses (including their applicability in humans for either somatic or heritable genome editing interventions) greatly increase their potential societal impacts and, as such, have brought an urgency to ethical and regulatory discussions about the application of such technology in our society. In this article, we explore different arguments (pragmatic, sociopolitical and categorical) that have been made in support of or in opposition to the new technologies of genome editing and their impact on the debate of the permissibility or otherwise of human heritable genome editing interventions in the future. For this purpose, reference is made to discussions on genetic engineering that have taken place in the field of bioethics since the 1980s. Our analysis shows that the dominance of categorical arguments has been reversed in favour of pragmatic arguments such as safety concerns. However, when it comes to involving the public in ethical discourse, we consider it crucial widening the debate beyond such pragmatic considerations. In this article, we explore some of the key categorical as well sociopolitical considerations raised by the potential uses of heritable genome editing interventions, as these considerations underline many of the societal concerns and values crucial for public engagement. We also highlight how pragmatic considerations, despite their increasing importance in the work of recent authoritative sources, are unlikely to be the result of progress on outstanding categorical issues, but rather reflect the limited progress on these aspects and/or pressures in regulating the use of the technology.

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The ability to alter a sequence of genetic material was initially developed in microorganisms during the 1970s and 1980s (for an overview: Walters et al., 2021 ). Since then, technological advances have allowed researchers to alter DNA in different organisms by introducing a new gene or by modifying the sequence of bases in the genome. The manipulation of the genome of living organisms (typically plants) continues a course that science embraced more than 40 years ago, and may ultimately allow, if not deliberately curtailed by societal decisions, the possibility of manipulating and controlling genetic material of other living species, including humans.

Genetic engineering can be used in a diverse range of contexts, including research (e.g., to build model organisms), pharmacology (e.g., for insulin production) and agriculture (e.g., to improve crop resistance to environmental pressures such as diseases, or to increase yield). Beyond these applications, modern genetic engineering techniques such as genome editing technologies have the potential to be an innovative tool in clinical interventions but also outside the clinical realm. In the clinical context, genome editing techniques are expected to help in both disease prevention and in treatment (Porteus, 2019 ; Zhang, 2019 ). Nevertheless, genome editing technology raises several questions, including the implications of its use for human germline cells or embryos, since the technology’s use could facilitate heritable genome editing interventions (Lea and Niakan, 2019 ). This possible use has fuelled a heated debate and fierce opposition, as illustrated by the moratoriums proposed by researchers and international institutions on the use of the technology (Lander et al., 2019 ; Baltimore et al., 2015 ; Lanphier et al., 2015 ). Heritable human germline modifications are currently prohibited under various legislations (Baylis et al., 2020 ; Ledford, 2015 ; Isasi et al., 2016 ; König, 2017 ) and surveys show public concerns about such applications, especially without clear medical justification (e.g., Gaskell et al., 2017 ; Jedwab et al., 2020 ; Scheufele et al., 2017 ; Blendon et al., 2016 ).

To analyse some implications of allowing heritable genome editing interventions in humans, it is relevant to explore underlying values and associated ethical considerations. Building on previous work by other authors (e.g., Coller, 2019 ; de Wert et al., 2018 ; van Dijke et al., 2018 ; Mulvihill et al., 2017 ; Ishii, 2015 ), this article aims to provide context to the debates taking place and critically analyse some of the major pragmatic, categorical and sociopolitical considerations raised to date in relation to human heritable genome editing. Specifically, we explore some key categorical and sociopolitical considerations to underline some of the possible barriers to societal acceptance, key outstanding questions requiring consideration, and possible implications at the individual and collective level. In doing so, we hope to highlight the predominance of pragmatic arguments in the scientific debate regarding the permissible use of heritable genome editing interventions compared to categorical arguments relevant to broader societal debate.

Human genome editing: a brief history of CRISPR/Cas9

Human genome editing is an all-encompassing term for technologies that are aimed at making specific changes to the human genome. In humans, these technologies can be used in embryos or germline cells as well as somatic cells (Box 1 ). Concerning human embryos or germline cells, the intervention could introduce heritable changes to the human genome (Lea and Niakan, 2019 ; Vassena et al., 2016 ; Wolf et al., 2019 ). In contrast, an intervention in somatic cells is not intended to result in changes to the genome of subsequent generations. It is worth noting that intergenerational effects occur only when the modified cells are used to establish a pregnancy which is carried to term. Thus, a distinction has been made between germline genome editing (GGE), which may only affect in vitro embryos in research activity, and heritable genome editing (HGE), which is used in reproductive medicine (e.g., Baylis et al., 2020 ). HGE could be used to prevent the transmission of serious genetic disease; however, other applications could be imagined, e.g., creating genetic resistance or even augmenting human functions.

In the last decade, prominent technical advances in genome engineering methods have taken place, including the zinc-finger nucleases (ZFNs) and TAL effector nucleases (TALENs), making human genome modification a tangible possibility (Gaj et al., 2013 ; Li et al., 2020 ; Gupta and Musunuru, 2014 ). In 2012, a study showed that the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), combined with an enzyme called Cas9, could be used as a genome‐editing tool in human cell culture (Jinek et al., 2012 ). In 2013, the use of CRISPR/Cas9 in mammalian cells was described, demonstrating the application of this tool in the genome of living human cells (Cong et al., 2013 ). In 2014, CRISPR/Cas9 germline modifications were first used in non-human primates, resulting in the birth of gene-edited cynomolgus monkeys (Niu et al., 2014 ). This was followed in 2015 by the first-ever public reported case of genome modification in non-viable human embryos (tripronuclear zygotes) (Liang et al., 2015 ). This study has caused broad concerns in the scientific community (Bosley et al., 2015 ) with leading journals rejecting publication for ethical reasons. Five years after these initial experiments were conducted, more than 10 papers have been published reporting the use of genome editing tools on human preimplantation embryos (for an overview: Niemiec and Howard, 2020 ).

Compared to counterpart genome technologies (e.g., ZFNs and TALENs), CRISPR/Cas9 is considered by many a revolutionary tool due to its efficiency and reduced cost. More specifically, CRISPR/Cas9 seems to provide the possibility of a more targeted and effective intervention in the genome involving the insertion, deletion, or replacement of genetic material (Dance, 2015 ). The potential applicability of CRISPR/Cas9 technique is considered immense, since it can be used on all type of organisms, from bacteria to plants, non-human cells, and human cells (Barrangou and Horvath, 2017 ; Hsu et al., 2014 ; Doudna and Charpentier, 2014 ; Zhang, 2019 ).

Box 1 Difference associated with germline cells and somatic cells.

For the purposes of the analysis presented in this article, one of the main differences is the heritability of genes associated with either type of cell. Germline cells include spermatozoa, oocytes, and their progenitors (e.g., embryonic cells in early development), which can give rise to a new baby carrying a genetic heritage coming from the parents. Thus, germline are those cells in an organism which are involved in the transfer of genetic information from one generation to the next. Somatic cells, conversely, constitute many of the tissues that form the body of living organisms, and do not pass on genetic traits to their progeny.

Germline interventions: the international debate

As a reaction to the 2015 study with CRISPR/Cas9, several commentaries by scientists were published regarding the future use of the technology (e.g., Bosley et al., 2015 ; Lanphier et al., 2015 ; Baltimore et al., 2015 ). Many of them focused on germline applications, due to the possibility of permanent, heritable changes to the human genome and its implications for both individuals and future generations. These commentaries included position statements calling for great caution in the use of genome editing techniques for heritable interventions in humans and suggested a voluntary moratorium on clinical germline applications of CRISPR/Cas9, at least until a broad societal understanding and consensus on their use could be reached (Brokowski, 2018 ; Baltimore et al., 2015 ; Lander, 2015 ). Such calls for a temporary ban were often seen as reminiscent of the “Asilomar ban” on recombinant DNA technology in the mid-1970s (Guttinger, 2017 ). Other commentaries asked for research to be discouraged or halted all together (Lanphier et al., 2015 ). More firmly, the United States (US) National Institutes of Health (NIH) released a statement indicating that the NIH would not fund research using genome editing technologies on human embryos (Collins, 2015 ).

In December 2015, the first International Summit on Human Gene Editing took place, hosted by the US National Academy of Sciences, the US National Academy of Medicine, the UK Royal Society, and the Chinese Academy of Sciences (NASEM). The organizing committee issued a statement about appropriate uses of the technology that included the following: “It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application” (NASEM, 2015 ).

Following this meeting, initiatives from different national bodies were organized to promote debate on the ethical issues raised by the new genome editing technologies and to work towards a common framework governing the development and permissibility of their use in humans. This included an ethical review published in 2016 by the Nuffield Council on Bioethics, addressing conceptual and descriptive questions concerning genome editing, and considering key ethical questions arising from the use of the technology in both human health and other contexts (Nuffield Council on Bioethics, 2016 ). In 2017, a committee on human genome editing set up by the US National Academy of Sciences (NAS) and the National Academy of Medicine (NAM) carried out a so-called consensus study “Human Genome Editing: Science, Ethics, and Governance” (NASEM, 2017 ). This study put forward a series of recommendations on policies and procedures to govern human applications of genome editing. Specifically, the study concluded that HGE could be justified under specific conditions: “In some situations, heritable genome editing would provide the only or the most acceptable option for parents who desire to have genetically related children while minimizing the risk of serious disease or disability in a prospective child” (NASEM, 2017 ). The report stimulated much public debate and was met with support and opposition since it was seen as moving forward on the permissibility of germline editing in the clinical context (Ranisch and Ehni, 2020 ; Hyun and Osborn, 2017 ).

Following the report in 2016, the Nuffield Council on Bioethics published a second report in 2018. Similar to the NASEM 2017 report, this report emphasizes the value of procreative freedom and stresses that in some cases HGE might be the only option for couples to conceive genetically related, healthy offspring. In this document, the Nuffield Council on Bioethics maintains that there are no categorical reasons to prohibit HGE. However, it highlights three kinds of interests that should be recognized when discussing prospective HGE. They are related to individuals directly affected by HGE (parents or children), other parts of society, and future generations of humanity. In this context, two ethical principles are highlighted as important to guide future evaluations of the HGE use in specific interventions: “(...) to influence the characteristics of future generations could be ethically acceptable, provided if, and only if, two principles are satisfied: first, that such interventions are intended to secure, and are consistent with, the welfare of a person who may be born as a consequence, and second, that any such interventions would uphold principles of social justice and solidarity (…)” (Nuffield Council on Bioethics, 2018 ). This report was met with criticism for (implicitly) advocating genetic heritable interventions might be acceptable even beyond the boundaries of therapeutic uses. This is particularly controversial and goes well beyond the position previously reached by the NASEM report (which limited permissible uses of genome editing at preventing the transmission of genetic variants associated to diseases) (Drabiak, 2020 ). On the other hand, others have welcomed the report and, within it, the identification of explicit guiding ethical principles helpful in moving forward the debate on HGE (Gyngell et al., 2019 ).

As a follow-up to the 2015 conference, a second International Summit on Human Gene Editing was scheduled for November 2018 in Hong Kong (National Academies of Sciences, Engineering, and Medicine, 2019 ). The event, convened by the Hong Kong Academy of Sciences, the UK Royal Society, the US National Academy of Sciences and the US National Academy of Medicine, was supposed to focus on the prospects of HGE. Just before the Summit began, news broke that He Jiankui, a Chinese researcher and invited speaker at the Summit, created the world’s first genetically edited babies resulting from the use of CRISPR/Cas9 in embryos (Regalado, 2018 ; Lovell-Badge, 2019 ). Although an independent investigation of the case is still pending, his experiments have now been reviewed in detail by some scholars (e.g., Greely, 2019 , 2021 ; Kirksey, 2020 ; Davies, 2020 ; Musunuru, 2019 ). These experiments were globally criticized, since they did not follow suitable safety procedures or ethical guidelines (Wang and Yang, 2019 ; Lovell-Badge, 2019 ; Krimsky, 2019 ), nor considered the recommendations previously put forward by international reports (NASEM, 2017 ; Nuffield Council on Bioethics, 2018 ) and legal frameworks (Araki and Ishii, 2014 ; Isasi et al., 2016 ). Different reactions were triggered, including another call by scientists for a global moratorium on clinical human genome editing, to allow time for international discussions to take place on its appropriate uses (Lander et al., 2019 ) or an outright ban on the technology (Botkin, 2019 ). There were also calls for a measured analysis of the possible clinical applications of human genome editing, without the imposition of a moratorium (Daley et al., 2019 ; Dzau et al., 2018 ).

Most countries currently have legal frameworks to ban or severely restrict the use of heritable genome editing technologies (Araki and Ishii, 2014 ; Isasi et al., 2016 ; Baylis et al., 2020 ). However, since He’s experiment, the possibility that researchers might still attempt (with some likelihood of success) to use the technology in human embryos, became a growing concern, particularly since some scientists have already announced their interest in further clinical experiments (Cyranoski, 2019 ). For many, He’s experiments highlighted the ongoing risks associated with the use of modern genome editing technology without proper safety protocols and regulatory frameworks at an international level (Ranisch et al., 2020 ). This has triggered the need to develop clear and strict regulations to be implemented if these tools are to be used in the future. This incident also led to the formation of several working groups, including the establishment of an international commission on the Clinical Use of Human Germline Genome Editing set up by the US National Academy of Medicine, the US National Academy of Sciences, and the UK’s Royal Society. In 2020, the commission published a comprehensive report on HGE, proposing a translational pathway from research to clinical use (National Academy of Medicine, National Academy of Sciences, and the Royal Society, 2020 ). Likewise, a global expert Advisory Committee was established by the World Health Organization (WHO) with the goal of developing recommendations on governance mechanisms for human genome editing. Although the committee insisted in an interim recommendation that “it would be irresponsible at this time for anyone to proceed with clinical applications of human germline genome editing” (WHO, 2019 ), it did not express fundamental concerns on the possibility that some forms of HGE will one day become a reality. In 2021, the WHO’s Advisory Committee issued some publications, including a “Framework for governance” report and a “Recommendations” report (WHO, 2021 ). Building on a set of procedural and substantive values and principles, the “Framework for Governance” report discusses a variety of tools and institutions necessary for developing appropriate national, transnational, and international governance and oversight mechanisms for HGE. Specifically, the report considers the full spectrum of possible applications of human genome editing (including epigenetic editing and human enhancement) and addresses specific challenges associated with current, possible and speculative scenarios. These range from somatic gene therapy for the prevention of serious hereditary diseases to potentially more controversial applications reminiscent of the He Jiankui case (e.g., the use of HGE in reproductive medicine outside regulatory controls and oversight mechanisms). Additionally, the “Recommendations” report proposes among other things whistleblowing mechanisms to report illegal or unethical research. It also highlights the need for a global human genome editing registry, that should also cover basic and preclinical research on different applications of genetic manipulation, including HGE. The report also emphasises the need of making possible benefits of human genome editing widely accessible.

The idea of a human genome editing registry has also been supported by the European Group on Ethics in Science and New Technologies (EGE), an advisory board to the President of the European Commission. After an initial statement on genome editing published in 2016, still calling for a moratorium on editing of human embryos (EGE, 2016 ), the EGE published a comprehensive Opinion in 2021 (EGE, 2021 ). Although the focus of this report is on the moral issues surrounding genome editing in animals and plants, HGE is also discussed. Similar to the WHO Advisory Committee, the EGE recommends for HGE not to be introduced prematurely into clinical application and that measures should be taken to prevent HGE’s use for human enhancement.

Overall, when reviewing reports and initiatives produced since 2015, common themes and trajectories can be identified. A key development is the observation that the acceptance of the fundamental permissibility of such interventions appears to be increasing. This constitutes an important change from previous positions, reflecting the fact that human germline interventions have long been considered a ‘red line’ or at least viewed with deep scepticism (Ranisch and Ehni, 2020 ). In particular, while there is agreement that it would be premature to bring HGE into a clinical context, key concerns expressed by authoritative international bodies and committees are now associated with acceptable uses of the technology, rather than its use per se. Consideration is now being given to the conditions and objectives under which germline interventions could be permissible, instead of addressing the fundamental question of whether HGE may be performed at all. The question of permissibility is often linked to the stage of technological development. These developments are remarkable, since the key ethical aspects of genome editing are now frequently confined to questions of safety or cost–benefit ratios, rather than categorical considerations.

Another common issue can also be found in recent reports: the question of involving society in the debate. There is consensus on the fact that the legitimacy and governance of HGE should not be left solely to scientists and other experts but should involve society more broadly. Since germline interventions could profoundly change the human condition, the need for a broad and inclusive public debate is frequently emphasized (Iltis et al., 2021 ; Scheufele et al., 2021 ). The most striking expression of the need for public engagement and a “broad societal consensus” can be found in the final statement by the 2015 International Summit on Human Gene Editing organizing committee, as previously quoted (NASEM, 2015 ). Furthermore, the EGE and others also stresses the need for an inclusive societal debate before HGE can be considered permissible.

The pleas for public engagement are, however, not free of tension. For example, the NASEM’s 2017 report was criticised for supporting HGE bypassing the commitment for the broad societal consensus (Baylis, 2017 ). Regarding HGE, some argue that only a “small but vocal group of scientists and bioethicists now endorse moving forward” (Andorno et al., 2020 ). Serious efforts to engage the public on the permissibility and uses of HGE have yet to be made. This issue not only lacks elaboration on approaches to how successful public participation can occur, but also how stop short of presenting views on how to translate the public’s views into ethical considerations and policy (Baylis, 2019 ).

Potential uses of heritable genome editing technology

HGE is expected to allow a range of critical interventions: (i) preventing the transmission of genetic variants associated with severe genetic conditions (mostly single gene disorders); (ii) reducing the risk of common diseases (mostly polygenic diseases), with the promise of improving human health; and (iii) enhancing human capabilities far beyond what is currently possible for human beings, thereby overcoming human limitations. The identification of different classes of potential interventions has shifted the debate to the applications considered morally permissible beyond the acceptable use of HGE (Dzau et al., 2018 ). Specifically, there are differences in the limits of applicability suggested by some of the key cornerstone publications discussed above. For example, the NASEM ( 2017 ) report suggests limiting the use of HGE to the transmission of genetic variants linked to severe conditions, although in a very regulated context. In a very similar way, the 2020 report from the International Commission on the Clinical Use of Human Germline Genome Editing suggests that the initial clinical use of HGE should be limited to the prevention of serious monogenic diseases. By contrast, the 2018 Nuffield Council on Bioethics Report does not seem to limit the uses of genome editing to specific applications, though suggests that applications should be aligned with fundamental guiding ethical principles and need to have followed public debate (Savulescu et al., 2015 ). The same report also discusses far-reaching and speculative uses of HGE that might achieve “other outcomes of positive value” (Nuffield Council on Bioethics, 2018 ). Some of these more speculative scenarios include “built-in genetic resistance or immunity to endemic disease”; “tolerance for adverse environmental conditions” and “supersenses or superabilities” (Nuffield Council on Bioethics, 2018 , p. 47).

There have been different views on the value of HGE technology. Some consider that HGE should be permissible in the context of therapeutic applications, since it can provide the opportunity to treat and cure diseases (Gyngell et al., 2017 ). For example, intervention in severe genetic disorders is considered as therapeutic and hence morally permissible, or even obligatory. Others consider HGE to be more like a public health measure, which could be used to reduce the prevalence of a disease (Schaefer, 2020 ). However, others maintain that reproductive uses of HGE are not therapeutic because there is no individual in a current state of disease which needs to be treated, rather a prospective individual to be born with a specific set of negative prospective traits (Rulli, 2019 ).

Below, HGE is discussed in the context of reproductive uses and conditions of clinical advantage over existent reproductive technologies. The HGE applications are explored regarding their potential for modifying one or more disease-related genes relevant to the clinical context. Other uses associated with enhancement of physical and mental characteristics, which are considered non-clinical (although the distinction is sometimes blurred), are also discussed.

Single gene disorders

An obvious application of HGE interventions is to prevent the inheritance of genetic variants known to be associated with a serious disease or condition. Its potential use for this purpose could be typically envisaged through assisted reproduction, i.e., as a process to provide reproductive options to couples or individuals at risk of transmitting genetic conditions to their offspring. Critics of this approach often argue that other assisted reproductive technologies (ARTs) and preimplantation screening technologies e.g., preimplantation genetic diagnosis (PGD), not involving the introduction of genetic modifications to germline cells, are already available for preventing the transmission of severe genetic conditions (Lander, 2015 ; Lanphier et al., 2015 ). These existent technologies aim to support prospective parents in conceiving genetically related children without the condition that affect them. In particular, PGD involves the creation of several embryos by in vitro fertilization (IVF) treatment that will be tested for genetic anomalies before being transferred to the uterine cavity (Sermon et al., 2004 ). In Europe, there is a range in the regulation of the PGD technology with most countries having restrictions of some sorts (Soini, 2007 ). The eligibility criteria for the use of PGD also vary across countries, depending on the range of heritable genetic diseases for which it can be used (Bayefsky, 2016 ).

When considering its effectiveness, PGD presents specific limitations, which include the rare cases in which either both prospective parents are homozygous carriers of a recessive genetic disease, or one of the parents is homozygous for a dominant genetic disease (Ranisch, 2020 ). In these cases, all embryos produced by the prospective parents will be affected by the genetic defect, and therefore it will not be possible to select an unaffected embryo after PGD. Currently, beyond adoption of course, the options available for these prospective parents include the use of a third-party egg or sperm donors.

Overall, given the rarity of cases in which it is not applicable, PGD is thought to provide a reliable option to most prospective parents for preventing severe genetic diseases to be transmitted to their offspring, except in very specific cases. HGE interventions have been suggested to be an alternative method to avoid single gene disorders in the rare cases in which selection techniques such as PGD cannot be used (Ranisch, 2020 ). It has also been proposed to use tools such as CRISPR/Cas9 to edit morphologically suitable but genetically affected embryos, and thus increase the number of embryos available for transfer (de Wert et al., 2018 ; Steffann et al., 2018 ). Moreover, HGE interventions are considered by some as a suitable alternative to PGD, even when the use of PGD could be possible. One argument in this respect is that, although not leading to the manifestation of the disease, the selected embryos can still be carriers of it. In this respect, differently from PGD, HGE interventions can be used to eliminate unwanted, potential future consequences of genetic diseases (i.e., by eliminating the critical mutation carried out in the selected embryo), with the advantage of reducing the risks of further propagation of the disease in subsequent future generations (Gyngell et al., 2017 ).

Overall, HGE interventions are thought to offer a benefit over PGD in some situations by providing a broader range of possible interventions, as well as by providing a larger number of suitable embryos. The latter effect is usually important in the cases where unaffected embryos are small in number, making PGD ineffective (Steffann et al., 2018 ). Whether these cases provide a reasonable ground to justify research and development on the clinical use of HGE remain potentially contentious. Some authors have suggested that the number of cases in which PGD cannot be effectively used to prevent transmission of genetic disorders is so marginal that clinical application of HGE could hardly be justified (Mertes and Pennings, 2015 ). Particularly when analyzing economic considerations (i.e., the allocation of already scarce resources towards clinical research involving expensive techniques with limited applicability) and additional risks associated with direct interventions. In either case of HGE being used as an alternative or a complementary tool to PGD, PGD will most likely still be used to identify those embryos that would manifest the disease and would hence require subsequent HGE.

The PGD technique, however, is not itself free of criticism and possible moral advantages of HGE over PGD have also been explored (Hammerstein et al., 2019 ; Ranisch, 2020 ). PGD remains ethically controversial since, identifying an unaffected embryo from the remaining embryos (which will not be used and ultimately discarded) amounts to the selection of ‘healthy’ embryos rather than ‘curing’ embryos affected by the genetic conditions. On the other hand, given a safe and effective application of the technology, the use of HGE is considered by many morally permissible to prevent the transmission of genetic variants known to be associated with serious illness or disability (de Miguel Beriain, 2020 ). One question that remains is whether HGE and PGD have a differing or equal moral permissibility or, at least, comparable. On issues including human dignity and autonomy, it was argued that HGE and PGD interventions can be considered as equally morally acceptable (Hammerstein et al., 2019 ). This equal moral status was, however, only valid if HGE is used under the conditions of existent gene variants in the human gene pool and to promote the child health’s best interest in the context of severe genetic diseases (Hammerstein et al., 2019 ). Because of selection and ‘therapy’, moral assessments resulted in HGE interventions being considered to some extent preferable to PGD, once safety is carefully assessed (Gyngell et al., 2017 ; Cavaliere, 2018 ). Specifically, PGD’s aim is selective and not ‘therapeutic’, which could be said to contradict the aims of traditional medicine (MacKellar and Bechtel, 2014 ). In contrast to PGD’s selectivity, HGE interventions are seen as ‘pre-emptively therapeutic’, and therefore closer to therapy than PGD (Cavaliere, 2018 ). However, it is also argued that HGE does not have curative aims, and thus it is not a therapeutic application, as there is no patient involved in the procedure to be cured (Rulli, 2019 ). On balance, there appears to be no consensus on which of the approaches, HGE and PGD, is morally a better strategy to prevent the transmission of single gene disorders, with a vast amount of literature expressing diverse positions when considering different scenarios (Delaney, 2011 ; Gyngell et al., 2017 ; Cavaliere, 2018 ; Ranisch, 2020 ; Rehmann-Sutter, 2018 ; Sparrow, 2021 ).

Polygenetic conditions

HGE is also argued to have the potential to be used in other disorders which have a polygenic disposition and operate in combination with environmental influences (Gyngell et al., 2017 , 2019 ). Many common diseases, which result from the involvement of several genes and environmental factors, fall into this category. Examples of common diseases of this type includes diabetes, coronary artery disease and different types of cancers, for which many of the genes involved were identified by studies of genome wide association (e.g., Wheeler and Barroso, 2011 ; Peden and Farral, 2011 ). These diseases affect the lives of millions of people globally, severely impacting health and often leading to death. Furthermore, these diseases have a considerable burden on national health systems. Currently, many of these diseases are controlled through pharmaceutical products, although making healthier life choices about diet and exercise can also contribute to preventing and managing some of them. Despite the interest, the use of PGD in polygenic conditions would hardly be feasible, due to the number of embryos needed to select the preferred genotype and available polygenic predictors (Karavani et al., 2019 ; Shulman and Bostrom, 2014 ).

In theory, HGE could be a potentially useful tool to target different genes and decrease the susceptibility to multifactorial conditions in current and future generations. The application of HGE to polygenic conditions is often argued by noting that the range of applicability of the technique (well beyond single gene disorders) would justify and outweigh the cost needed to develop it. However, to do so, a more profound knowledge of genetic interactions, of the role of genes and environmental factors in diverse processes would be needed to be able to modify such interconnected systems with limited risk to the individual (Lander, 2015 ). Besides, it is now understood that, depending on the genetic background, individuals will have different risks of developing polygenetic diseases (risk-associated variants), but hardly any certainty of it. In other words, although at the population level there would most likely be an incidence of the disease, it is not possible to be certain of the manifestation of the disease in any specific individual. As a result, the benefits of targeting a group of genes associated to a disease in a specific individual would have to be assessed in respect to the probability of incidence of the disease. The risk-benefit ratio for HGE is considerably increased for polygenic conditions compared to monogenic disorders. Additionally, the risks of adverse effects, e.g., off-target effects, increases with the number of genes targeted for editing. The latter effects make the potential benefits of HGE in polygenic diseases more uncertain than in single gene disorders.

Genetic enhancement

A widespread concern regarding the use of HGE is that such interventions could be used not only to prevent serious diseases, but also to enhance desirable genetic traits. Currently, our knowledge on how to genetically translate information into specific phenotypes is very limited and some argue that it might never be technically feasible to achieve comprehensive genetic enhancements using current gene editing technologies (Janssens, 2016 ; Ranisch, 2021 ). Similar to many diseases, in which different genetic and other factors are involved, many of the desirable traits to be targeted by any enhancement will most likely be the result of a combination of several different genes influenced by environment and context. Moreover, the implications for future generations of widespread genetic interventions in the human population and its potential impact on our evolutionary path are difficult to assess (Almeida and Diogo, 2019 ). Nevertheless, others argue that genetic enhancement through HGE could be possible in the near future (de Araujo, 2017 ).

There has been much discussion regarding the meaning of the terms and the conceptual or normative difference between ‘therapy’ and ‘enhancement’ (for an early discussion: Juengst, 1997 ; Parens, 1998 ). There are mainly three different meanings of ‘enhancement’ used in the literature. First, ‘enhancement’ is sometimes used to refer to measures that go beyond therapy or prevention of diseases, i.e., that transcend goals of medicine. Second, ‘enhancement’ is used to refer to measures that equip a human with traits or capacities that they typically do not possess. In both cases, the term points to equally controversial and contrasting concepts: on the one hand, those of ‘health’, ‘disease’ or ‘therapy’, and on the other, those of ‘normality’ or ‘naturalness’. Third, ‘enhancement’ is sometimes also used as an umbrella-term describing all measures that have a positive effect on a person’s well-being. According to this definition, the cure, or prevention of a disease is then also not opposed to an enhancement. Here again, this use refers to the controversial concept of ‘well-being’ or a ‘good life’.

It is beyond the scope of this article to provide a detailed review of the complex debate about enhancement (for an overview: Juengst and Moseley, 2019 ). However, three important remarks can be made: first, although drawing a clear line between ‘enhancement’ and ‘therapy’ (or ‘normality’, etc.) will always be controversial, some cases can be clearly seen as human enhancement. This could include modifications to augment human cognition, like having a greater memory, or increasing muscle mass to increase strength, which are not considered essential for human health (de Araujo, 2017 ).

Second, it is far from clear whether a plausible account of human enhancement would, in fact, be an objectivist account. While authors suggest that there is some objectivity regarding the conditions that constitute a serious disease (Habermas, 2003 ), the same might not be true for what constitutes an improvement of human functioning. It may rather turn out that an enhancement for some might be seen as a dis-enhancement for others. Furthermore, the use of the HGE for enhancement purposes can be considered at both an individual and a collective level (Gyngell and Douglas, 2015 ; Almeida and Diogo, 2019 ), with a range of ethical and biological implications. If HGE is to be used for human enhancement, this use will be in constant dependence on what we perceive as ‘normal’ functioning or as ‘health’. Therefore, factors such as cultural and societal norms will have an impact on where such boundaries are drawn (Almeida and Diogo, 2019 ).

Third, it should be noted that from an ethical perspective the conceptual question of what enhancement is, and what distinguishes it from therapy, is less important than whether this distinction is ethically significant in the first place. In this context, it was pointed out that liberal positions in bioethics often doubt that the distinction between therapy and enhancement could play a meaningful role in determining the limits of HGE (Agar, 1998 ). The consideration of genetic intervention for improving or adding traits considered positive by individuals have raised extreme positions. Some welcome the possibility to ameliorate the human condition, whilst others consider it an alarming attempt to erase aspects of our common human ‘nature’. More specifically, some authors consider HGE a positive step towards allowing humans the opportunity to obtain beneficial traits that otherwise would not be achievable through human reproduction, thus providing a more radical interference in human life to overcome human limitations (de Araujo, 2017 ; Sorgner, 2018 ). The advocates of this position are referred to as ‘bioliberals’ or ‘transhumanists’ (Ranisch and Sorgner, 2014 ), and its opponents are referred to as ‘bioconservatives’ (Fukuyama, 2002 ; Leon, 2003 ; Sandel, 2007 ). Transhumanism supports the possibility of humans taking control of their biology and interfering in their evolution with the use of technology. Bioconservatism defends the preservation and protection of ‘human essence’ and expresses strong concerns about the impact of advanced technologies on the human condition (Ranisch and Sorgner, 2014 ).

For the general public, HGE used in a clinical context seems to be less contentious compared when used as a possible human enhancement tool. Specifically, some surveys indicate that the general-public typically exhibits a reduced support for the use of genome editing interventions for enhancement purposes compared to therapeutic purposes (Gaskell et al., 2017 ; Scheufele et al., 2017 ). In contrast, many technologies and pharmaceutical products developed in the medical context to treat patients are already being used by individuals to ‘enhance’ some aspect of their bodies. Some examples include drugs to boost brain power, nutritional supplements, and brain-stimulating technologies to control mood, even though their efficiency and safety is not clear. This could suggest that views on enhancement may vary depending on the context and on what is perceived as an enhancement by individuals. It may be informative to carry out detailed population studies to explore whether real ethical boundaries and concerns exist, or whether these are purely the result of the way information is processed and perceived.

Heritable genome editing: Mapping the ethical debate

Even though genome editing methods have only been developed in the last decade, the normative implication of interventions into the human germline have been discussed since the second half of the 20th century (Walters et al., 2021 ). Some even argue that, virtually, all the ethical issues raised by genetic engineering were already being debated at that time (Paul, 2005 ). This includes questions about the distinction between somatic and germline interventions, as well as between therapy and enhancement (e.g., Anderson, 1985 ). Nevertheless, as it has been widely noted, it is difficult to draw clear lines between these two categories (e.g., McGee, 2020 ; Juengst, 1997 ), and alternative frameworks have been proposed, particularly in the context of HGE (Cwik, 2020 ). Other questions include the normative status of human nature (e.g., Ramsey, 1970 ), the impossibility of consent from future generations (e.g., Lappe, 1991 ), possible slippery slopes towards eugenics (e.g., Howard and Rifkin, 1977 ), or implications for justice and equality (e.g., Resnik, 1994 ).

When discussing the ethics of HGE, roughly three types of considerations can be distinguished: (i) pragmatic, (ii) sociopolitical, and iii) categorical (Richter and Bacchetta, 1998 ; cf. Carter, 2002 ). Pragmatic considerations focus on medical or technological aspects of HGE, such as the safety or efficacy of interventions, risk–benefit ratio, possible alternatives or the feasibility of responsible translational research. Such considerations largely depend on the state of science and are thus always provisional. For example, if high-risk technologies one day evolve into safe and reliable technologies, some former pragmatic considerations may become obsolete. Sociopolitical aspects, on the other hand, are concerned with the possible societal impact of technologies, e.g., how they can promote or reduce inequalities, support or undermine power asymmetries, strengthen, or threaten democracy. Similar to pragmatic considerations, sociopolitical reasons depend on specific contexts and empirical factors. However, these are in a certain sense ‘outside’ the technology—even though technologies and social realities often have a symbiotic relationship. While sociopolitical considerations can generate strong reasons against (or in favour of) implementing certain technologies, most often these concerns could be mitigated by policies or good governance. Categorical considerations are different and more akin to deontic reasons. They emphasise categorical barriers to conduct certain deeds. It could be argued, for instance, that the integrity of the human genome or the impossibility to obtain consent from future generation simply rule out certain options to modify human nature. Such categorical considerations may persist despite technological advances or changing sociopolitical conditions.

Comparing the bioethical literature on genetic engineering from the last century with the ongoing discussions shows a remarkable shift in the ethical deliberation. In the past, scholars from the field of medical ethics, as well as policy reports, used to focus on possible categorical boundaries for germline interventions and on possible sociopolitical consequences of such scenarios. For instance, the influential 1982 report “Splicing Life” from the US President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioural Research prominently discussed concerns about ‘playing God’ against the prospects of genetically engineering human beings, as well as possible adverse consequences of such interventions. Although this study addresses potential harms, pragmatic arguments played only a minor role, possibly due to the technical limitations at the time.

With the upcoming availability of effective genome editing techniques, the focus on the moral perspective seems to have been reversed. Increasingly, the analysis of the permissibility of germline interventions is confined to questions of safety and efficacy. This is demonstrated by the 2020 consensus study report produced by an international commission convened by the US National Academy of Medicine, the US National Academy of Sciences, and the UK’s Royal Society, which aimed at defining a translational pathway for HGE. Although the report recognizes that HGE interventions does not only raise pragmatic questions, ethical aspects were not explicitly addressed (National Academy of Medicine, National Academy of Sciences, and the Royal Society, 2020 ).

Similarly, in 2019, a report on germline interventions published by the German Ethics Council (an advisory body to the German government and parliament) emphasizes that the “previous categorical rejection of germline interventions” could not be maintained (Deutscher Ethikrat, 2019 , p. 5). The German Ethics Council continues to address ethical values and societal consequences of HGE. However, technical progress and the development of CRISPR/Cas9 tools seem to have changed the moral compass in the discussion about germline interventions.

For a comprehensive analysis of HGE to focus primarily on pragmatic arguments such as safety or efficacy would be inadequate. In recent years, developments in the field of genome editing have occurred at an incredibly fast pace. At the same time, there are still many uncertainties about the efficacy of the various gene editing methods and unexpected effects in embryo editing persist (Ledford, 2015 ). Social and political implication also remain largely unknown. To date, it has been virtually impossible to estimate how deliberate interventions into the human germline could shape future societies and to conduct a complete analysis of the safety aspects of germline interventions.

Moreover, as the EGE notes, we should be cautious not to limit the complex process of ethical decision-making to pragmatic aspects such as safety. The “‘safe enough’ narrative purports that it is enough for a given level of safety to be reached in order for a technology to be rolled out unhindered, and limits reflections on ethics and governance to considerations about safety” (EGE, 2021 , p. 20). Consequently, the EGE has highlighted the need to engage with value-laden concepts such as ‘humanness’, ‘naturalness’ or ‘human diversity’ when determining the conditions under which HGE could be justified. Even if a technology has a high level of safety, its application may still contradict ethical values or lead to undesirable societal consequences. Efficacy does not guarantee compatibility with well-established ethical values or cultural norms.

While concepts such as ‘safety’ or ‘risk’ are often defined in scientific terms, this does not take away the decision of what is ethically desirable given the technical possibilities. As Hurlbut and colleagues put it in the context of genome editing: “Limiting early deliberation to narrowly technical constructions of risk permits science to define the harms and benefits of interest, leaving little opportunity for publics to deliberate on which imaginations need widening, and which patterns of winning and losing must be brought into view” (Hurlbut et al., 2015 ). Therefore, if public engagement is to be taken seriously, cultural norms and values of those affected by technologies must also be considered (Klingler et al., 2022 ). This, however, means broadening the narrow focus on pragmatic reasons and allowing categorical as well as sociopolitical concerns in the discourse. Given the current attention on pragmatic reasons in current debates on HGE, it is therefore beneficial to revisit the categorical and sociopolitical concerns that remain unresolved. The following sections provide an overview of relevant considerations that can arise in the context of HGE and that underline many of the societal concerns and values crucial for public engagement.

Human genome ‘integrity’

Heritability seems to be one of the foremost considerations regarding germline genome editing, as it raises relevant questions on a ‘natural’ human genome and its role in ‘human nature’ (Bayertz, 2003 ). This follows an ongoing philosophical debate on ‘human nature’, at least as defined by the human genome. This has ensued a long debate on the value of the human genome and normative implications associated with its modification (e.g., Habermas, 2003 ). Although a comprehensive discussion of these topics goes beyond the scope of this paper, the human genome is viewed by many as playing an important role in defining ‘human nature’ and providing a basis for the unity of the human species (for discussion: Primc, 2019 ). Considering the implications for the individual and the collective, some affirm the right of all humans to inherit an unmodified human genome. For some authors, germline modification is considered unethical, e.g., a “line that should not be crossed” (Collins, 2015 ) or a “crime against humanity” (Annas et al., 2002 ).

The Universal Declaration on the Human Genome and Human Rights (UDHGHR) states that “the human genome underlies the fundamental unity of all members of the human family, as well as the recognition of their inherent dignity and diversity. In a symbolic sense, it is the heritage of humanity” (Article 1, UNESCO, 1997 ). The human genome is viewed as our uniquely human collective ‘heritage’ that needs to be preserved and protected. Critics of heritable genetic interventions argue that germline manipulation would disrupt this natural heritage and therefore would threaten human rights and human equality (Annas, 2005 ). Heritable human genome editing creates changes that can be heritable to future generations. For many, this can represent a threat to the unity and identity of the human species, as these modifications could have an impact on the human’s gene pool. Any alterations would then affect the evolutionary trajectory of the human species and, thus, its unity and identity.

However, the view of the human genome as a common heritage is confronted with observations of the intrinsic dynamism of the genome (Scally, 2016 ). Preservation of the human genome, at least in its current form, would imply that the genome is static. However, the human genome is dynamic and, at least in specific periods of environmental pressure, must have naturally undergone change, as illustrated by human evolution (Fu and Akey, 2013 ). The genome of any individual includes mutations that have occurred naturally. Most of them seem to be neither beneficial nor detrimental to the ability of an individual to live or to his/her health. Others can be detrimental and limiting to their wellbeing. It has been shown that, on average, each human genome has 60 new mutations compared to their parents (Conrad et al., 2011 ). At the human population level, a human genome can have in average 4.1–5 million variants compared to the ‘reference’ genome (Li and Sadler, 1991 ; Genomes Project C, 2015 ). The reference genome itself is thus a statistical entity, representing the statistic distribution of the probability of different gene variants in the whole genome. Human genomic variation is at the basis of the differences in the various physical traits present in humans (e.g., eye colour, height, etc.), as well as specific genetic diseases. Thus, the human population is comprised of genomes with a pattern of variants and not of ‘one’ human genome that needs to be preserved (Venter et al. 2001 ). The human genome has naturally been undergoing changes throughout human history. An essentialist view of nature seems to be the basis for calling for the preservation of genome integrity. However, in many ways, this view is intrinsically challenged by the interpretation portrayed by evolutionary biology of our genetic history already more than a century ago. Nevertheless, despite the dynamic state of the human genome, this in itself cannot justify the possibility of modifying the human genome. It is also worth considering that the integrity of the human genome could also be perceived in a ‘symbolic’ rather than biological literal meaning. Such an interpretation would not require a literally static genome over time, but instead suggest a boundary between ‘naturally’ occurring variation and ‘artificially’ induced change. This is rather a version of the ‘natural’/unnatural argument, rather than an argument for a literally unchanged genetic sequence.

The modification of the human genome raises complex questions about the characterization of the human species genome and if there should be limits on interfering with it. The options to modify the human genome could range from modifying only the genes that are part of the human gene pool (e.g., those genes involved in severe genetic diseases such as Huntington’s disease) to adding new variants to the human genome. Regarding variants which are part of the common range of variation found in the human population (although it is not possible to know all the existent variations), the question becomes whether HGE could also be used in any of them (e.g., even the ones providing some form of enhancement) or only in disease-associated variants and thus be restricted to the prevention of severe genetic diseases. In both cases, the integrity of the human genome is expected to be maintained with no disruption to human lineage. However, it could be argued that this type of modification is defending a somewhat conservative human nature argument, since it is considering that a particular genetic make-up is ‘safe’ or would not involve any relevant trade-offs. In contrast, a different conclusion could be drawn on the integrity of the human genome when introducing genotypical and phenotypical traits that do not lie within the common range of variation found in the population (Cwik, 2020 ). In all cases, since the implications of the technology are intergenerational and consequently, it will be important to carry out an assessment of the risks that we, as a species, are willing to take when dealing with disease and promoting health. For this, we will need to explore societal views, values and cultural norms associated with the human genome, as well as possibly existing perceptions of technology tampering with ‘nature’. To support such an assessment, it would be useful to draw on a firm concept of human nature and the values it implies, beyond what is implied by genetic aspects.

Human dignity

In several of the legally binding and non-binding documents addressing human rights in the biomedical field, human dignity is one of the key values emphasized. There are concerns that heritable genome interventions might conflict with the value of human dignity (Calo, 2012 ; Melillo, 2017 ). The concerns are considered in the context of preserving the human genome (Nordberg et al. 2020 ). More specifically, the recommendation on Genetic Engineering by the Council of Europe (1982) states that “ the rights to life and to human dignity protected by Articles 2 and 3 of the European Convention on Human Rights imply the right to inherit a genetic pattern which has not been artificially changed” (Assembly, 1982 ). This is supported by the Oviedo Convention on Human Rights and Biomedicine (1997), where Article 13 prohibits any genetic intervention with the aim of introducing a modification in the genome of any descendants. The Convention is the only international legally binding instrument that covers human germline modifications among the countries which have ratified it (Council of Europe, 1997 ). However, there have been some authors disputing the continued ban proposed by the Oviedo Convention (Nordberg et al. 2020 ). Such authors have focused on the improvements of safety and efficacy of the technology in contrast to authors focusing on its value for human dignity (Baylis and Ikemoto, 2017 ; Sykora and Caplan, 2017 ). The latter authors seem to highlight the concept of human dignity to challenge heritable interventions to the human genome.

But a question in debate has been to demonstrate how ‘human dignity’, described in such norms, relates to heritable genome interventions. The concept of the human genome as common genetic heritage, distinguishing humans from other species seems one of the main principles implied by such norms. In this view, the human genome determines who belongs to the human species and who does not, and thus confers an individual the dignity of being a human by association. This creates an inherent and strong link between the concept of human genome and the concept of human dignity and its associated legal rights (Annas, 2005 ). It could be argued that a genetic modification to an individual may make it difficult for him/her to be recognized as a human being and therefore, preservation of the human genome being important for human dignity to be maintained. This simple approach, or at least interpretation, however, ignores the fact that the human genome is not a fixed or immutable entity, as exemplified by human evolution (as discussed in the previous section). As a result, the view that HGE interventions are inherently inadmissible based on the need to preserve human dignity is contested (Beriain, 2018 ; Raposo, 2019 ). More broadly, the idea that biological traits are the basis for equality and dignity, supporting the need for the human genome to be preserved, is often challenged (Fenton, 2008 ).

It is argued that to fully assess the impact of the HGE interventions on human dignity, it will be necessary to have a better understanding of the concept of human dignity in the first place (Häyry, 2003 ; Cutas, 2005 ). For some, however, human dignity is a value that underlies questions of equality and justice. Thus, the dignity-based arguments could uncover relevant questions in the discussion of ethical implications on modifying the human genome (Segers and Mertes, 2020 ). In the Nuffield Council on Bioethics Report (2018) principles of social justice and solidarity, as well as welfare, are used to guide the debate on managing HGE interventions. Similarly, the concept of human dignity could, therefore, provide the platform upon which consideration of specific values could be discussed, broaden the debate on HGE to values shared by society.

Right of the child: informed consent

In many modern societies, every individual, including children, have the rights to autonomy and self-determination. Therefore, each person is entitled to decide for themselves in decisions relating to their body. These rights are important for protecting the physical integrity of a person. When assessing the implication of allowing individuals to take (informed) decisions relative to the use of heritable genetic interventions on someone else’s body, it is useful to reflect on the maturity of existing medical practices and, more broadly, on the additional complexities associated with the heritability of any such intervention.

In modern health-care systems, informed consent provides the opportunity for an individual to exercise autonomy and make an informed decision about a medical procedure, based on their understanding of the benefits and risks of such procedure. Informed consent is thus a fundamental principle in medical (research) ethics when dealing with human subjects (Beauchamp and Childress, 2019 ).

Heritable genome interventions present an ethical constraint on the impossibility of future generations of providing consent to an intervention on their genome (Smolenski, 2015 ). In other words, future generations cannot be involved in a decision which could limit their autonomy, since medical or health-related decisions affecting them are placed on the present generation (and, in the case of a child to be born, more specifically, on his/her parents). However, many other actions taken by parents of young children also intentionally influence the lives of those children and have been doing so for millennia (Ranisch, 2017 ). Although these actions may not involve altering their genes, many of such actions can have a long-lasting impact on a child’s life (e.g., education and diet). However, it could be argued that they do not have the irreversible effect that HGE will have in the child and future generations. In cases where parents act to expand the life choices of their children by eliminating disease (e.g., severe genetic diseases), this would normally be thought to outweigh any possible restriction on autonomy. In these cases, if assuming HGE benefits will outweigh risks regarding safety and efficacy, the use of HGE could be expected to contribute to the autonomy of the child, as him/her would be able in the future to have a better life, not constrained by the limitations of the disease. As a result, even if it is accepted that these technologies may in one way reduce the autonomy of future generations, some believe that this will often be outweighed by other effects increasing autonomy (Gyngell et al., 2017 ). In other words, it is reasonable to suppose that, when taken by parents based on good information and understanding of risks and impacts, the limitation in the autonomy of unborn children associated with heritable genetic interventions would be compensated by the beneficial effects of increasing their autonomy when born (Gyngell et al., 2017 ).

It has often been emphasized that possible genetic interventions must not curtail the future possibilities of offspring to live their lives according to their own idea of a good life. This view originated in the liberal tradition and is associated with the “right to an open future”, defended by Joel Feinberg ( 1992 ). That is an anticipatory autonomy right that parents can violate, even though the offspring could exercise it only in the future. Feinberg has discussed the right to an open future in the context of religious education. However, various authors have applied this argument to the question of permissible and desirable genetic interventions (Buchanan et al., 2000 ; Glover, 2006 ; Agar, 1998 ). Accordingly, germline modifications or selection would have to allow the offspring to have a self-determined choice of life plans. It would therefore be necessary to provide offspring with genetic endowments that represent the so-called all-purpose goods. These goods are “useful and valuable in carrying out nearly any plan of life or set of aims that humans typically have” (Buchanan et al., 2000 , p. 167). While this claim is certainly appealing, in reality it will be difficult to identify phenotypes that will only broaden and do not narrow the spectrum of life plans. Take, for example, body size: a physique favourable for a basketball player would at the same time be less favourable in successfully riding horses as a professional jockey and vice versa. Increasing some opportunities often means reducing other ones.

The arguments of informed consent and open future need to be explored outside the realm of severe genetic diseases by considering other scenarios (including scenarios of genetic enhancement). Hereby, the effects of the interventions on the autonomy of future generations can be assessed more comprehensively. As for enhancement, decisions outside the realm of health can be more controversial, as the traits that parents see fit to generate enhancement may inadvertently condition a child’s choices in the future in an undesirable way.

If HGE is to be used, questions on how the consent and information should be provided to parents to fully equip them to decide in the best interests of the child will need to be assessed (Evitt et al., 2015 ). This is evident if considering the informed consent used in the study conducted by He Jiankui. One of the many criticisms of the study was the inadequacy of the informed consent process provided to the parents, which did not meet regulatory or ethical standards (Krimsky, 2019 ; Kirksey, 2020 ). This raises questions on how best to achieve ethical and regulatory compliance regarding informed consent in applications of HGE (Jonlin, 2020 ).

Discrimination of people with disabilities

For many years, there has been an effort to develop selective reproduction technologies to prevent genetic diseases or conditions leading to severe disabilities. These forms of reproductive genetic disease prevention are based on effectively filtering and eradicating embryos or foetuses affected by genetic diseases. There are divergent views regarding the use of these technologies. For example, the disability rights movement argues that the use of technologies such as prenatal testing (PNT) and PGD discriminates against people living with a disability (Scully, 2008 ; Asch and Barlevy, 2012 ). The key arguments presented supporting this view are: (i) the limited value of a genetic trait in respect to the life of an embryo (Parens and Asch, 2000 ) and (ii) the ‘expressivist’ argument (Buchanan, 1996 ; Shakespeare, 2006 ). The first argument is based on the critique that a disabling trait is viewed as being more significant than the life of an embryo/foetus. This argument was initially used in the context of prenatal testing and selective termination, and has also been applied in the context of new technologies like PGD (Parens and Asch, 2000 ). The second, the ‘expressivist’ argument, argues that the use of these technologies expresses negative or discriminatory views on the disabling conditions they are targeting and subsequently on the people living with these conditions (Asch and Wasserman, 2015 ). The expressivist argument, however, has been challenged by stressing the importance of differentiating between the disability itself and the people living with disability (Savulescu, 2001 ). The technology’s use is aimed at reducing the incidence of disability, and it does not have a position of value on the people that have a specific condition.

When applying the same arguments to the use of HGE in comparison with other forms of preventing heritable genetic diseases, some important considerations can be made. Regarding the first argument, in contrast to selective reproduction technologies, HGE may allow the removal of the disabled trait with the aim of ensuring survival of the affected embryo. However, most likely, PGD would be used before and after the editing of the embryos to help the identification of the ones requiring intervention and verifying the efficiency of the genetic intervention (de Miguel Beriain, 2018 ; Ranisch, 2020 ). Similarly, the expressivist argument continues to be challenged if the application of human HGE is envisaged in the context of severe genetic diseases (e.g., Tay-Sachs and Huntington’s disease). It has been argued that the choice to live without a specific genotype neither implies discriminating people living with a respective condition nor considering the life of people living with the disease not worth living or less valuable (Savulescu, 2001 ). In other words, the expressivist argument is not a valid or a sufficiently strong ethical argument for prospective parents not to have the option to have a future child without a genetic disease.

It is worth noting that the debate on the use of reproduction technologies for the prevention of genetic diseases is not at all new, and that modern HGE techniques only serve to highlight ethical concerns that have been expressed for a long time. In the case of preventing genetic diseases, the application of both arguments to HGE intervention could be considered not to provide sufficiently strong ethical arguments to limit the use of the technology in the future. However, it is worth exploring whether scientific innovations like HGE are either ameliorating or reinvigorating ethical concerns expressed so far, for example in creating a future that respects or devalues disability as a part of the human condition. Perhaps even more importantly, given their potential spectrum of possible intervention and efficacy, it is important to reflect on whether the broad use of HGE could have an impact on concepts of disability and ‘normality’ as a whole distorting an already unclear ethical line between clinical and non-clinical interventions. Moreover, research work exploring the relationship between disability and identity indicated that personhood with disability can be an important component to people’s identity and interaction with the world. In the case of heritable human genome editing, it is not yet known how this technology will impact the notions of identity and personhood in people who had their germline genome modified (Boardman and Hale, 2018 ). For further progress on these issues public engagement might be important to gather different views and perceptions on the issue.

Justice and equality

Beside the limits of applicability, another common ethical concern associated with the use of genome editing technologies, as with many new technologies, is the question of accessibility (Baumann, 2016 ). Due to the large investments that will need to be made for continuing development of the technology, there is a (perceived) risk of it becoming an expensive technology that only a few wealthy individuals in any population (and/or only citizens in comparatively rich countries) can access. In addition, there is concern that patenting of genome editing technologies will delay widespread access or lead to unequal distribution of corresponding benefits (Feeney et al., 2018 ). This may, consequently, contribute to further increases in existing disparities, since individuals or countries with the means of accessing better health treatments may have economic advantages (Bosley et al., 2015 ). This could enhance inequality at different levels, depending on the limits of applicability of the technology. Taken to its extreme, the use of the technology could allow germline editing to create and distinguish classes of individuals that could be defined by the quality of their manipulated genome.

The concern that the possibility of germline interventions in humans could entrench or even increase inequalities has accompanied the discussion about ethics of genetic interventions from the very beginning until today (e.g. Resnik, 1994 ). In ‘Remaking Eden’ Lee Silver envisioned a divided future society, consisting of a genetically enhanced class, the “genRich”, and a genetic underclass, the “naturals” (Silver, 1997 ). Françoise Baylis recently echoed such concerns regarding future HGE interventions, namely that “unequal access to genome-editing technologies will both accentuate the vagaries of the natural lottery and introduce an unjust genetic divide that mirrors the current unjust economic and social divide between rich and poor individuals” (Baylis, 2019 , p. 67). At the same time, the possibility to genetically intervene in the ‘natural lottery’ has also been associated with the hope of countering natural inequalities and increase equality of opportunities. Robert Sinsheimer may be among the first to envision such a ‘new’ individualistic type of ‘eugenics’ that “would permit in principle the conversion of all of the unfit to the highest genetic level” (Sinsheimer, 1969 , p. 13). More recently, in the book ‘From chance to choice: Genetics and justice’ (2000) it is argued that “equality of opportunity will sometimes require genetic interventions and that the required interventions may not always be limited to the cure or prevention of disease” (Buchanan et al., 2000 , p. 102). When discussing issues related to justice and equality, it will be important to involve a broad spectrum of stakeholders to better evaluate the economic effects of the commercialization of the technology.

Conclusions

With ongoing technological developments and progress with guiding and regulating its acceptable use, the possibility of HGE interventions in the human genome is closer than ever to becoming a reality. The range of HGE applicability can go from preventing the transmission of genetic variants associated with severe genetic conditions (mostly single gene disorders but also, to a lesser extent, polygenic diseases) to genetic enhancements. The permissibility of HGE has often been considered on the basis of possible uses, with therapeutic uses generally considered more acceptable than non-therapeutic ones (including human enhancement). When compared with other technologies with similar therapeutic uses (e.g., PGD) already in use, HGE presents similarities and differences. However, from an ethical acceptability perspective, there is currently no consensus on whether HGE is more or less acceptable than PGD.

An important conclusion of this study is that, along with the technological development of genome germline editing techniques, a shift in the focus of analyses on its applicability has been observed. More specifically, the emphasis on pragmatic considerations seems to have increased substantially compared with the previous emphasis on categorical and sociopolitical arguments. Many of the most recent publications from authoritative advisory committees and institutions discuss the permissibility of HGE interventions primarily on the basis of pragmatic arguments, in which safety and efficacy are the main focus. Since germline interventions could profoundly change the human condition, the need for a broad and inclusive public debate on this topic has also been frequently emphasized. However, limited consideration has been given to approaches to carry out such action effectively, and on how to consider their outcomes in relevant policies and regulations.

It is currently not entirely clear whether: (i) the pragmatic position championed by such authoritative sources builds on the premise that the ethical debate has reached sufficient maturity to allow a turning point; (ii) the lack of progress has somewhat hampered further consideration of issues still considered controversial; (iii) regulatory pressure is somewhat de facto pushing forward the introduction of such technologies despite critical, unresolved ethical issues. Based on the analysis presented in this paper, a combination of the latter factors (ii and iii) seems more likely. In engaging the public in societal debates on the acceptability of such technologies, unresolved questions are likely to re-emerge. Specifically, it is possible that categorical and sociopolitical considerations will gain renewed focus during public engagement. In other words, when involving the public in discussions on HGE, it is possible that cultural values and norms, not only questions of safety and efficacy, will re-emerge as crucial to the acceptance of the technology (What is meant by natural? What is understood by humanity? etc.).

HGE interventions put into question specific biological and moral views of individuals, including views on the value of the human genome, on human dignity, on informed consent, on disability and on societal equality and justice. The range of ethical issues affected by the introduction of such technology, often still characterised by non-convergent, and at times conflicting, positions, illustrate the importance of further consideration of these issues in future studies and public engagement activities. As a result, society’s moral uncertainties will need to be assessed further to support the regulation of HGE technologies and form a well-informed and holistic view on how they can serve society’s common goals and values.

Data availability

This statement is not applicable.

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This work was supported by Fundação para Ciência e a Tecnologia (FCT) of Portugal [UIDP/00678/2020 to M.A]. We thank Dr. Michael Morrison for his comments and Dr. Gustav Preller for his proofreading of this manuscript.

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Almeida, M., Ranisch, R. Beyond safety: mapping the ethical debate on heritable genome editing interventions. Humanit Soc Sci Commun 9 , 139 (2022). https://doi.org/10.1057/s41599-022-01147-y

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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.”

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:

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.”

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.”

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.”

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.”

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.”

To learn more:

Technology and Public Purpose project, Belfer Center for Science and International Affairs, Harvard Kennedy School of Government, https://www.belfercenter.org/tapp/person

Concluding statement from the Second International Summit on Human Genome Editing. http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=11282018b

A global observatory for gene editing: Sheila Jasanoff and J. Benjamin Hurlbut call for an international network of scholars and organizations to support a new kind of conversation. https://www.nature.com/articles/d41586-018-03270-w

Building Capacity for a Global Genome Editing Observatory: Institutional Design. http://europepmc.org/abstract/MED/29891181

Glenn Cohen’s blog: How Scott Gottlieb is Wrong on the Gene Edited Baby Debacle. http://blog.petrieflom.law.harvard.edu/2018/11/29/how-scott-gottlieb-is-wrong-on-the-gene-edited-baby-debacle/

Gene-Editing: Interpretation of Current Law and Legal Policy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651701/

Forum: Harvard T.H. Chan School of Public Health event on the promises and challenges of gene editing, May 2017: https://theforum.sph.harvard.edu/events/gene-editing/

Petrie-Flom Center Annual Conference: Consuming Genetics: Ethical and Legal Considerations of New Technologies: http://petrieflom.law.harvard.edu/events/details/2019-petrie-flom-center-annual-conference

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