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Mad Scientists Genetically
Re-engineer Human Embryos!

July 21, 2015

For the first time, scientists have announced the genetic modification of human embryos (germline modification), in a study conducted by researchers from Sun Yat-sen University in Guangzhou, China, and published in the journal Protein & Cell.

Previously, scientists have limited themselves to modifying the genomes of adult cells, largely due to ethical concerns and concerns over potential side effects.

Indeed, the new paper did conclude that genome modification of embryos still faces serious safety obstacles.

"I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale," said stem-cell researcher George Daley of Harvard Medical School, who was not involved in the research. "Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes."

Shockingly high mutation rate

In order to partially allay ethical concerns, the experiment was performed on non-viable embryos obtained from fertility clinics. These embryos could never lead to a live birth, even if implanted.

The researchers sought to modify the gene responsible for a potentially fatal blood disorder known as s-thalassaemia. They used a gene editing technique called CRISPR/Cas9, which has been successfully used to modify the genomes of adult cells in the past. The technique consists of injecting the target cells with the CRISPR/Cas9 enzyme complex, programmed to target (remove) a specific gene. At the same time, another molecule is injected which is programmed to insert a new gene in place of the removed ones.

The researchers injected 86 single-celled human embryos with the molecules, then waited 48 hours for them to multiply into about eight cells each. Only 71 embryos survived the process, and only 54 of these were genetically tested. The original gene was successfully removed in only 24, and in only a few of these did the replacement gene take root.

"If you want to do it in normal embryos, you need to be close to 100 percent," lead researcher Junjiu Huang said. "That's why we stopped. We still think it's too immature."

In addition, the process led to a surprising number of mutations, caused by CRISPR/Cas9 targeting the wrong part of the gene. The mutation rate was much higher than seen in mouse embryos or adult human cells.

Huang warned that because only a small part of the genome was tested, the mutation rate was probably even higher than reported.

Scientists call for moratorium

The paper was preceded for months by rumors, which led to a March editorial in the journal Nature, calling for a moratorium on germline modification.

Existing gene therapies modify genes only in adult cells, and therefore are more limited in their effects. This may restore certain functions to a damaged organ, for instance, but is less likely to cause major changes to other types of cells than germline modification.

In contrast, a fertilized egg (zygote) eventually multiplies and differentiates into every cell in the adult organism. Modifying the genome of this cell causes changes in the organism-wide genome, and can potentially change the function of every organ in the body. In addition, such changes are passed on to future generations, by definition without their consent. It is also impossible to fully understand the long-term effects these modifications could have, across the generations.

Any germline modification, many ethicists have also warned, opens up a slippery slope toward attempts to "improve" the human genome, such as the creation of "designer babies." The uses of germline modification are so potentially broad, that the risk of unethical uses is enormous.

Other germline modification studies, however, are already underway elsewhere in China.

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