‘Designer babies’ free of diabetes and heart disease soon?:US scientists achieve precise human embryo DNA editing breakthrough

Scientists at Columbia University have successfully edited the DNA of early human embryos with a level of accuracy not achieved before. The breakthrough could one day help prevent inherited diseases, but it has also reignited concerns about the possibility of creating babies with selected traits. The research was led by geneticist Dieter Egli, who said the findings should encourage public discussion about the benefits and risks of altering human embryo DNA. “We can provide the scientific data, but society must decide how such technology should be used,” he said. New gene-editing method more efficient for DNA modification The researchers used a newer technique known as base editing. Unlike traditional CRISPR gene editing, which cuts DNA strands, base editing makes small, precise changes to individual genetic letters. According to the team, this method avoided the extensive DNA damage often seen with earlier gene-editing techniques. However, Dr Egli stressed that many questions remain unanswered, particularly regarding possible side effects. He said the technology is not ready for clinical use. The study has been published online and is currently being reviewed for publication in a scientific journal. Gene editing has been debated for more than a decade The debate over editing human embryos began after the development of CRISPR technology in 2012. CRISPR allowed scientists to target and alter specific parts of DNA quickly and cheaply. It soon became a widely used research tool and led to efforts to develop treatments for inherited diseases. In 2023, the US Food and Drug Administration approved a CRISPR-based treatment for sickle cell anaemia. However, scientists also discovered that CRISPR was not always accurate. In some cases, it failed to target the correct DNA sequence or caused unintended genetic changes. Previous embryo experiments raised safety concerns In 2018, Chinese scientist He Jiankui used CRISPR to alter the DNA of human embryos, claiming he wanted to make children resistant to HIV infection. The experiment was widely condemned by scientists and ethicists, and Chinese authorities later sentenced him to three years in prison. He later claimed the experiment resulted in three healthy children, but independent experts have never verified their condition. In 2020, Dr Egli’s team conducted its own CRISPR experiment on human embryos carrying a gene mutation linked to inherited blindness. The researchers hoped embryos would repair the faulty gene using a healthy copy as a template. While some embryos succeeded, many experienced serious genetic damage. Some lost large sections of DNA, while others lost entire chromosomes. “It had absolutely catastrophic consequences,” Dr Egli said. The findings strengthened concerns that embryo gene editing was too risky for practical use. Base editing produces more accurate results To overcome these problems, scientists turned to base editing, a technique developed in 2016 by Harvard geneticist David Liu and colleagues. Rather than cutting DNA, base editing creates a small nick in one DNA strand and guides the cell to correct the mutation. The method has already shown promise. Last year, doctors used customised base-editing molecules to cure a baby with a potentially fatal genetic disorder. Dr Egli’s team decided to test the technology on human embryos. Researchers successfully edited two important genes The scientists focused on two genes. One gene, PCSK9, is linked to levels of LDL cholesterol and the risk of heart disease. The second gene, HBG, plays a role in foetal haemoglobin production. Using donated fertilised eggs and two-cell embryos, the researchers introduced base-editing molecules and successfully altered both genes. In some embryos, they were able to edit both genes at the same time. Unlike earlier CRISPR experiments, the researchers did not observe major DNA damage. Challenges remain before clinical use Although the results were encouraging, the process was not perfect. In some cases, the editing molecules failed to reach their target. As a result, some cells in the same embryo were edited while others remained unchanged. This created so-called “mosaic” embryos, containing different genetic versions of the same gene. Such differences could potentially cause medical problems if the embryos developed into babies. Dr Paula Amato, a fertility specialist at Oregon Health Science University who was not involved in the study, described the results as promising but said further review would be necessary. Bioethicist Ana Iltis of Wake Forest University warned that some harmful effects might not become apparent until after birth. Potential benefits for IVF patients Nathan Treff, chief clinical officer at Nucleus Genomics and a co-author of the study, said the technology could eventually help IVF patients. The method may allow doctors to repair disease-causing mutations in embryos that would otherwise be discarded. “There is still work to do before getting to that point, but this research moves us closer,” he said. Nucleus Genomics will help support future stages of the research because US federal funding does not cover studies involving human embryos. Future research will focus on reducing mosaicism and testing the technology on more developed embryos containing around 100 cells. Debate grows over genetic selection Nucleus Genomics, founded in 2021, already screens IVF embryos for thousands of genetic disorders. The company also estimates the future risk of conditions such as heart disease and diabetes and analyses genes linked to traits including height and intelligence. The company attracted controversy after advertising in New York’s subway system with the slogan “Have your best baby.” Critics argue that predictions about complex traits such as intelligence remain unreliable and have accused the company of promoting a modern form of eugenics. The company rejects those claims. A spokesperson said the company sees itself as helping bring advanced genetic technologies into future medical care. Experts warn of ethical and safety risks Some scientists remain concerned about the long-term implications of editing human embryos. Geneticist Fyodor Urnov of the University of California, Berkeley, said the results were scientifically impressive but argued that existing IVF screening methods are already safe and effective. He questioned whether it was worth introducing a technology that still carries significant uncertainties. Urnov also warned that the research could eventually be used by people seeking to enhance traits rather than prevent disease. “What they are really doing is providing the ‘baby improvers’ with a how-to manual,” he said. Scientists say limits still exist Despite concerns, Dr Egli believes the technology may eventually allow a small number of genetic changes to be made safely in embryos. However, he noted that the more genes scientists attempt to edit at once, the greater the risk of failure. “I think you can probably combine three or four, maybe even five, but there is a limit,” he said. “Where that limit is remains to be determined.” For now, researchers say the technology remains experimental, and major scientific, medical and ethical questions must still be answered before any clinical use can be considered.