Gene-edited babies are now closer to becoming a reality. The ethical debate is far from settled
Pioneering gene editing therapies are already in clinical use, saving lives and ease the pain devastating genetic diseases. However, the number of patients receiving these treatments is increasing, and the risk of passing disease-causing mutations to their children remains.
Scientific consensus—and law in 70 countries – has long recognized that using a powerful technique for human germline editing, the process of manipulating human embryo DNA to avoid genetic diseases and prevent their transmission from one generation to the next, is too dangerous.
But new research has found that it is now possible to edit the DNA of human embryos with unprecedented precision; This suggests that human germline editing may be possible in the relatively near future. But scientists have warned that significant hurdles remain before we reach the point where it is possible to safely engineer viable human embryos.
“Six years ago, I thought the use of gene editing in human embryos was a non-starter,” said Amander Clark, professor of molecular cell and developmental biology at the University of California, Los Angeles and director of the UCLA Center for Reproductive Science, Health and Education.
“This study reopens the possibility that therapeutic gene editing may be possible with IVF embryos in the future,” Clark, who was not involved in the research, said via email.
Laboratory research on human embryos, usually donated in vitro fertilization It is strictly regulated in most countries and is usually only allowed for a certain period of time. 14 days after the creation of the embryo. It is also unclear how supportive public attitudes toward gene-edited babies are; Beyond medical safety issues, skepticism largely stems from ethical questions around the potential use of this cutting-edge technology to create “designer babies” whose genes have been edited or deliberately selected for desired traits.
Sharpening a dull tool
Katarina Harasimov performs basic editing in the Niakan laboratory at the Loke Trophoblast Research Center at the University of Cambridge. – Loke Trophoblast Research Centre, University of Cambridge
The gene editing technique known as CRISPR-Cas9 is used in laboratories around the world and is revolutionizing scientific research, allowing scientists to edit the genes of living organisms for biotechnology and medical research. Two scientists who designed the technology in 2020 won the Nobel Prize in chemistryand in 2023, US Food and Drug Administration approved The first two gene therapies for sickle cell disease, a debilitating and life-shortening inherited red blood cell disorder that disproportionately affects African Americans.
But in some ways, CRISPR-Cas9 is a blunt tool. When the technology edits DNA, it creates a double-strand break in the target region of the strand, and when used to modify human embryos, several studies have shown that this leads to major and undesirable changes. possibly even loss of an entire chromosome.
The potential for unknown health effects is one reason the scientific community condemned work by Chinese researcher He Jiankui in 2018, which revealed the existence of two girls born from embryos he said he had modified using CRISPR-Cas9 to make them resistant to HIV. he took three years imprisonment It has only since been published in 2019. He did not respond to a request for comment.
Changing a single DNA letter
A newer, more precise form of CRISPR, known as basic editingIt can change a single letter (or base) of DNA at a time.
Base editing was first used in a 2022 clinical trial. changing immune cells A teenager in the United Kingdom after doctors exhausted all other options to treat his form of leukemia. Eight other children and two adults I continued to receive treatment. Last year, doctors used base editing to treat a baby born with severe CPS1 deficiency, a rare and dangerous genetic disease.
Now, two new studies have used this technique to edit human embryos donated for research purposes by people undergoing IVF treatment at the earliest stages of development. Both teams found that the precision of the technique reduced the likelihood of unwanted chromosomal abnormalities.
Kathy Niakan, professor of reproductive physiology and director of the Loke Trophoblast Research Center at the University of Cambridge, and her team used this technique to better understand how an important gene in human embryo development works. They discovered that a gene called NANOG, named after the legendary Celtic Tír na nÓg, or land of the always young, plays a key role in how the first embryonic cells that will eventually develop into the fetus and placenta are formed. The study was published In the scientific journal Nature on June 25.
In the normal embryo (left), the magenta-stained cells will develop into the placenta, the yellow cells into the yolk sac, and the cyan blue cells into the epiblast, which will later form the body. In the embryo (right) where base editing was used to block the NANOG gene, no cyan cells can be seen. – Katarina Harasimov et al/Loke Trophoblast Research Centre, University of Cambridge
Niakan said base editing represents a significant advance over traditional CRISPR-Cas9 because it has a much lower risk of causing unwanted chromosome errors. “Base editing can precisely change one nucleotide base pair to another across the entire human genome, which consists of approximately 3 billion base pairs – this is an incredible feat,” he explained.
In a separate study, Dietrich Egli, an associate professor of developmental cell biology at Columbia University, used base editing to introduce one of two genetic mutations into newly fertilized eggs. One targeted the gene known as PCSK9, which regulates cholesterol, and the other targeted HBG, which encodes the fetal form of hemoglobin, an oxygen-carrying protein. He chose these two genes because they are well-studied targets in nonheritable gene editing. Egli said a peer-reviewed scientific journal conditionally accepted study.
While both studies represent a step toward heritable gene editing, Egli said it’s still a long way from being used in a clinical setting. Although base editing does not appear to cause major chromosomal damage, at least two significant disadvantages remain.
Egli, Niakan and their team found that some of the embryos they edited exhibited what they described as “mosaicism,” when the intended editing was not effective in all cells. In addition, they both found some “off-target” effects where unwanted genes were altered. This poses a risk in editing the human embryo because that embryo will give birth to every cell in the body.
“This is a long staircase with many different steps and perhaps some plateaus in between,” Egli said. he said. “We started from the bottom and have made a few steps in that direction, but I think we can look at the progress that has been made and discuss the pros and cons of going further.”
Images of an early human embryo base edited to block the NANOG gene in the first week after fertilization. – Oliver Bower et al/Loke Trophoblast Research Centre, University of Cambridge
Helen O’Neill, associate professor of reproductive and molecular genetics at the Institute of Women’s Health at University College London, said genome editing in human embryos had value in allowing scientists to understand the rules that govern the earliest stages of human life. He did not participate in either study.
“This may help us understand why so many embryos in IVF fail to develop, arrest, implant or progress despite appearing morphologically acceptable,” O’Neill said in the statement.
“In the long term, it may help us think more clearly and compassionately about the very small group of patients with serious hereditary conditions for whom preimplantation genetic testing is not sufficient.”
O’Neill added that the debate around embryo editing is often framed as the only possible endpoint being designer babies. “This framing misses true scientific and clinical value,” he noted.
Concerns about designer babies
Laurie Zoloth, a professor of religion and ethics at the University of Chicago, stated that the research once again fueled the ethical debate about altering human embryos, stating that editing embryos is risky and therefore should remain banned for now only for safety reasons, except for use in scientific research. He noted that there are already ways to prevent having babies with genetic abnormalities; using genetic screening before conception and during pregnancy, and testing embryos before implantation during IVF.
“The mosaicism problem is not solved; they don’t really understand the long-term effects of the intervention; and there is no way to have a trial pregnancy without an actual pregnancy and child,” she said in an email.
He added that there are also longer-term theological and philosophical issues about “designing” babies to have desirable characteristics.
“These are even more profound when they appear to be designing babies who will be at lower risk for cardiovascular problems in the long distant future, which can be resolved with lifestyle choices and can already be fully treated with medications in the hypothetical future.”
While it’s defensible to edit embryos to prevent conditions such as Tay-Sachs, a fatal neurological disease that occurs in the first few months of life, he said there could be “a slippage between treatment and enhancement,” a situation that could lead to what Zoloth calls the “Gattaca problem,” after the 1997 movie that imagines a society obsessed with genetic perfection and dictated by that perfection.
“Could this path lead us to an even more unjust and unjust future, with the children of the richest and the children of the poor who lack resources and cannot compete in democracy?” he said.
Zoloth noted that knowledge of how human genetics affects physical traits and behavior is still very limited. “On the one hand, it is striking that we have the capacity to spend so much resources and attention on changing the genetic code of the embryo in exactly the direction we think is normal or optimal, when we cannot figure out how to ensure that children when they are born have clean, safe and engaging primary schools with well-paid teachers.” he added.
A. Newly released survey on public attitudes The survey into research on human embryos in four countries found that the majority of respondents in the UK, Netherlands and Spain supported the use of genome editing on embryos to help pregnancy occur by eliminating a serious or life-threatening condition. However, in Italy this figure was 46%.
Zoloth noted that bioethicists have a duty to think and ask questions, but banning science also has risks.
“We don’t want to ban the investigation,” he said. “That’s why it’s important to put guardrails in place for new science and is protective of both research and society.”
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