Australasian Science: Australia's authority on science since 1938

Second Genetically Modified Human Embryos Created

By AusSMC

A second case of gene editing of human embryos has attempted to introduce resistance to HIV infection, but only four of the 26 embryos were modified successfully.


“These Chinese researchers are trying to perfect the art of modifying genetic expression in human embryos. It follows on from a similar publication last year, also from China, which demonstrated... that genetic changes can be made but cannot be controlled. The implication is that if the embryo was implanted and a baby eventually born, the genetic makeup would be uncertain.

“This is very different from pre-implantation genetic testing carried out in Australia and other countries, which allows selection of a normal embryo during in vitro fertilisation for couples who both carry genes for a disorder, such as cystic fibrosis. There is no genetic manipulation with this method.

“For ethical reasons, the embryos used were abnormal, and not likely ever to develop into a foetus if implanted in the uterus. That in itself raises the question of whether the outcome of the experiments has clinical relevance, as others have previously shown that abnormal gametes are most unlikely to develop into a normal embryo.”

Professor Bernie Tuch is Director of the NSW Stem Cell Network and an Honorary Professor at the University of Sydney.


“This paper is clearly looking toward human reproductive uses of this technology, about which there has been insufficient national and international discussion and debate, both within the scientific community and between the scientific community and the general public, and about which there is no consensus.

“Even if it is ultimately determined in some jurisdictions that this technology is appropriate for use in human reproduction, it is unclear whether enhancement applications, such as introducing HIV resistance, will be among the approved uses. HIV can currently be both prevented and effectively treated, raising the question of whether it is an appropriate target for human germline genome editing, in particular in advance of applications to mitigate or avoid serious early-onset disease.

“This paper, as with the 2015 paper, demonstrates the difficulties of applying CRISPR/Cas9 to human embryos, though imperfectly given the triploid status of the embryos used... Work on normal human embryos, focused on questions of basic human biology, is more likely to produce useful data.”

Dr Debra Mathews is Assistant Director of Science Programs at the Johns Hopkins Berman Institute of Bioethics, USA.


“The paper is very similar to the previous work published in Protein & Cell, in that embryos not suitable for reproductive purposes were used for the experiments. The embryos used in this report inherited an entire extra haploid genome from the father, whereas normal embryos will only inherit one haploid genome from the mother and one haploid genome from the father. The consequences of this additional genetic material on the accuracy and efficiency of human embryo genome editing is unclear, and this paper provides no insight into this important question... Viable embryos donated to research are the only option for addressing the efficacy and improving the accuracy of gene editing in human embryos.

“The newly published work was performed with institutional ethics approval, and further confirms that the field does not have the correct technical know-how to begin proof-of-principle experiments to correct genes in pre-implantation embryos for therapeutic benefit. Critically, no gene-edited embryos were used to make a baby. Making a baby from gene-edited embryos by transferring the edited embryos to a woman’s uterus is a very bright ethical line that should not be crossed until the technology is proven safe and following an open discussion as to the benefit to society.”

Dr Amander Clark is Professor of Molecular, Cell and Developmental Biology at the University of California, Los Angeles, USA.


“This paper is the second publication to describe attempts at modifying the human germline... The new study attempts to edit a gene involved in HIV. Some people have naturally occurring mutations in the CCR5 gene which render those individuals resistant to HIV infection. Thus, using gene editing to create individuals with the CCR5 mutation would provide natural protection against HIV.

“The new study follows essentially the same path as the first study; using the CRISPR/Cas9 gene-editing system in tripro­nuclear embryos that are discarded by fertility clinics. Patients attending such clinics gave permission to donate these embryos for research.

“The results are both comforting and disturbing. The good news is that the technique worked for this group in the same way that it did for the first group. This indicates the reproducibility of the science... [and] should inspire confidence in the public. However, this group of researchers also reproduced another finding described by the first group, namely that this type of gene editing also causes off-target effects.

“Notwithstanding the use of tripronuclear embryos that clearly aren’t the same as normal embryos that can develop properly, the salutary lesson is that there is still much to be learned about gene editing in human embryos before it is ready for prime time. Studies in mice and non-human primates will undoubtedly be informative but ultimately it will be studies like the ones just published using donated human embryos that will give us the most understanding.”

Dr Peter Donovan is Professor of Biological Chemistry and of Developmental and Cell Biology at the University of California, Irvine, USA.


The original paper in the Journal of Assisted Reproduction and Genetics can be downloaded from http://tinyurl.com/jzh3xbp