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A technique of “gene correction” eliminates a mutation in human embryos causing fatal heart defects.

The controversial new work, published in the journal Nature, was accomplished by a team from Oregon Health and Science University and the Salk Institute.

CRISPR allowed the team to target a single mutation that causes cardiomyopathy – and caused a permanent, or “germ-line” genetic change that can be passed onto future generations.

The success could prevent millions of cases of disease in the future, the scientists contend. But how, when – and whether – the practice will actually be clinically applied is a question for ethicists and institutional review boards.

“The ethical considerations of moving this technology to clinical trials are complex and deserve significant public engagement before we can answer the broader question of whether it’s in humanity’s interest to alter human genes for generations,” said Daniel Dorza, the senior vice president for research at Oregon Health and Science University, who was not one of the authors.

“By using this technique, it’s possible to reduce the burden of this heritable disease on the family and eventually the human population,” said Shoukhrat Mitalipov, senior author, also from OHSU.

The mutation of gene MYBPC3 affects men and women of all ages. The donated human eggs and sperm cells carried the mutation. To avoid uneven genetic changes, the team worked at the earliest stages of fertilization and development (the oocyte) to make sure all the eventual cells would show the same elimination of the mutation – even when paired with one unhealthy gene.

“Our technology successfully repairs the disease-causing mutation by taking advantage of a DNA repair response unique to early embryos,” said Hun Wu, a Salk scientists and one of the authors.

But even the scientists involved in the latest work acknowledge there are reasons for caution as the work progresses.

“Gene editing is still in its infancy so even through this preliminary effort was found to be safe and effective, it is crucial that we continue to proceed with the utmost caution, paying the highest attention to ethical considerations,” said Juan Carlos Izpisua Belmonte, a Salk corresponding author. 

The news of the successful gene editing technique was first reported last week. But the details of the gene targeted, and the nature of the successful “correction” were published Wednesday.

The limits to genetic engineering of human cells have not been established, at international or even national levels. The U.S. had not engaged in the kinds of boundary pushing of China and Sweden – until now.

Nonetheless, an American report published in February urged the need to progress forward with the research.

“Human Genome Editing: Science, Ethics and Governance” was published by the National Academy of Science, a publication that two years to produce. The Committee on Human Gene Editing recommended a series of general values: transparency, wellbeing of people, fairness, and responsible science, in an age of DNA manipulation. They explicitly urged caution when it came to “germ-line” editing, since the heritable changes should be considered for compelling reasons. Overall, their recommendation was that genetic engineering should be tightly regulated – and it should focus on treating disease and not enhancing the human species.

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