Should Gene Editing Be Performed on Human Embryos?

The most potent use of the new gene editing technique CRISPR is also the most controversial: tweaking the genomes of human embryos to eliminate genes that cause disease.

By John Harris, Marcy Darnovsky
Published 27 Nov 2018, 09:25 GMT
Photograph by Art by Thomas Porostocky
On November 25, 2018, geneticist He Jiankui of China's Southern University of Science and Technology announced that his lab had successfully used the Crispr-Cas9 gene-editing system to make the world's first genetically edited human babies. Outside scientists haven't verified his claims, and his home university is planning to investigate him for academic violations. But if the results hold, the experiment would mark a scientific milestone— and raise profound ethical issues. In the August 2016 issue of National Geographic magazine, we invited contributors to weigh the ethics of making edits to the human genome that future generations would inherit.

Pro: Research on Gene Editing in Humans Must Continue

By John Harris

John Harris is professor emeritus in science ethics at University of Manchester, U.K., and the author of How to be Good, Oxford University Press 2016.

In February of this year, the Human Fertilisation and Embryology Authority in the United Kingdom approved a request by the Francis Crick Institute in London to modify human embryos using the new gene editing technique CRISPR-Cas9. This is the second time human embryos have been employed in such research, and the first time their use has been sanctioned by a national regulatory authority. The scientists at the Institute hope to cast light on early embryo development—work which may eventually lead to safer and more successful fertility treatments.

The embryos, provided by patients undergoing in vitro fertilisation, will not be allowed to develop beyond seven days. But in theory—and eventually in practice—CRISPR could be used to modify disease-causing genes in embryos brought to term, removing the faulty script from the genetic code of that person’s future descendants as well. Proponents of such “human germline editing” argue that it could potentially decrease, or even eliminate, the incidence of many serious genetic diseases, reducing human suffering worldwide. Opponents say that modifying human embryos is dangerous and unnatural, and does not take into account the consent of future generations. Who is right?

Let’s start with the objection that embryo modification is unnatural, or amounts to playing God. This argument rests on the premise that natural is inherently good. But diseases are natural, and humans by the millions fall ill and die prematurely—all perfectly naturally. If we protected natural creatures and natural phenomena simply because they are natural, we would not be able to use antibiotics to kill bacteria or otherwise practice medicine, or combat drought, famine, or pestilence. The health care systems maintained by every developed nation can aptly be characterised as a part of what I have previously called “a comprehensive attempt to frustrate the course of nature.” What’s natural is neither good nor bad. Natural substances or natural therapies are only better that unnatural ones if the evidence supports such a conclusion.

The matter of consent has been raised by Francis Collins, director of the National Institutes of Health. “Ethical issues presented by altering the germline in a way that affects the next generation without their consent,” he has said, constitute “strong arguments against engaging in” gene editing.

This makes no sense at all. We have literally no choice but to make decisions for future people without considering their consent. All parents do this all the time, either because the children are too young to consent, or because they do not yet exist. George Bernard Shaw and Isadora Duncan knew this. When, allegedly, she said to him “why don’t we make a baby together … with my looks and your brains it cannot fail” she was proposing a deliberate germline determining decision in the hope of affecting their future child. Shaw’s more sober response—“Yes but what if it has my looks and your brains!”—identifies a different possible, but from the child’s perspective equally non-consensual, outcome. Rightly, neither Shaw nor his possible partner thought their decision needed to wait for the consent of the resulting child.

Needless to say, parents and scientists should think responsibly, based on the best available combination of evidence and argument, about how their decisions will affect future generations. However, their decision-making simply cannot include the consent of the future children.

Finally, there’s the argument that modifying genomes is inherently dangerous because we can’t know all the ways it will affect the individual. But those who fear the risks of gene editing don’t take into account the inherent dangers in the 'natural' way we reproduce. Two-thirds of human embryos fail to develop successfully, most of them within the first month of pregnancy. And every year, 7.9 million children—6 percent of total births worldwide—are born with a serious defect of genetic or partially genetic origin. Indeed so risky is unprotected sex that, had it been invented as a reproductive technology rather than found as part of our evolved biology, it is highly doubtful it would ever have been licensed for human use.

Certainly we need to know as much as possible about the risks of gene-editing human embryos before such research can proceed. But when the suffering and death caused by such terrible single-gene disorders as cystic fibrosis and Huntington’s disease might be averted, the decision to delay such research should not be made lightly. Just as justice delayed is justice denied, so, too, therapy delayed is therapy denied. That denial costs human lives, day after day.

Con: Do Not Open the Door to Editing Genes in Future Humans

By Marcy Darnovsky

Marcy Darnovsky, Ph.D., is executive director of the Centre for Genetics and Society. She speaks and writes on the politics of human biotechnology.

The gene editing tool known as CRISPR catapulted into scientific laboratories and headlines a few short years ago. Fast on its heels came the re-emergence of a profoundly consequential controversy. Should these new techniques be used to engineer the traits of future children, who would pass their altered genes to all the generations that follow?

This is not an entirely new question. The prospect of creating genetically modified humans was openly debated back in the late 1990s, more than a decade and a half before CRISPR came on the scene and several years before the human genome had been fully mapped.

It wasn’t long before we saw provocative headlines about designer babies. Princeton mouse biologist Lee Silver, writing in Time magazine in 1999, imagined a fertility clinic of the near future that offered “Organic Enhancement” for everyone, including people with “no fertility problems at all.” He even wrote the ad copy: “Keep in mind, you must act before you get pregnant. Don't be sorry after she's born. This really is a once-in-a-lifetime opportunity for your child-to-be.”

During the same millennial shift, policymakers in dozens of countries came to a very different conclusion about the genetic possibilities on the horizon. They wholeheartedly supported gene therapies that scientists hoped (and are still hoping) can safely, effectively, and affordably target a wide a range of diseases. But they rejected human germline modification—using genetically altered embryos or gametes to produce a child—and in some 40 countries, passed laws against it.

The issue of human germline modification stayed on a slow simmer during the first decade of the 21st century. But it roared to a boil in April 2015, when researchers at Sun Yat-sen University announced they had used CRISPR to edit the genomes of nonviable human embryos. Their experiment was not very successful in technical terms, but it did focus the world’s attention.

In December 2015, controversy about using CRISPR to produce children was a key agenda item at the International Summit on Human Gene Editing organised by the national science academies of the United States, the United Kingdom, and China. Nearly every speaker agreed that at present, making irreversible changes to every cell in the bodies of future children and all their descendants would constitute extraordinarily risky human experimentation. By all accounts, far too much is unknown about issues including off-target mutations (unintentional edits to the genome), persistent editing effects, genetic mechanisms in embryonic and fetal development, and longer-term health and safety consequences.

Conversations about putting new gene editing tools into fertility clinics need to begin with an obvious but often overlooked point. By definition, germline gene editing would not treat any existing person’s medical needs. At best, supporters can say that it might re-weight the genetic lottery in favour of different outcomes for future people—but the unknown mechanisms of both CRISPR and human biology suggest that unforeseeable outcomes are close to inevitable.

Beyond technical issues are profound social and political questions. Would germline gene editing be justifiable, in spite of the risks, for parents who might transmit an inherited disease? It’s certainly not necessary. Parents can have children unaffected by the disease they have or carry by using third-party eggs or sperm, an increasingly common way to form families. Some heterosexual couples may hesitate to use this option because they want a child who is not just spared a deleterious gene in their lineage, but is also genetically related to both of them. They can do that too, with the embryo screening technique called pre-implantation genetic diagnosis (PGD), a widely available procedure used in conjunction with in vitro fertilisation.

PGD itself raises social and ethical concerns about what kind of traits should be selected or de-selected. These questions are particularly important from a disability rights perspective (which means they’re important for all of us). But screening embryos for disease is far safer for resulting children than engineering new traits with germline gene editing would be. Yet this existing alternative is often omitted from accounts of the controversy about gene editing for reproduction.

It is true that a few couples—a very small number—would not be able to produce unaffected embryos, and so could not use PGD to prevent disease inheritance. Should we permit germline gene editing for their sake? If we did, could we limit its use to cases of serious disease risk?

From a policy perspective, how would we draw the distinction between a medical and enhancement purpose for germline modification? In which category would we put short stature, for example? We know that taller people tend to earn more money. So do people with paler skins. Should arranging for children with financially or socially 'efficient' varieties of height and complexion be considered medical intervention?

Think back to the hypothetical fertility clinic offering 'Organic Enhancement' as a “once-in-a-lifetime opportunity for your child-to-be.” Think back to the 1997 movie Gattaca, about a society in which the genetically enhanced—merely perceived to be biologically superior—are born into the physical reality of those whom we might now call the one percent. These are fictional accounts, but they are also warnings of a possible human (or not so human) future. The kinds of social changes they foresee, once set in motion, could be as difficult to reverse as the genetic changes we’re talking about.

In opening the door to one kind of germline modification, we are likely to open it to all kinds. Permitting human germline gene editing for any reason would likely lead to its escape from regulatory limits, to its adoption for enhancement purposes, and to the emergence of a market-based eugenics that would exacerbate already existing discrimination, inequality, and conflict. We need not and should not risk these outcomes.

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