“These Chinese researchers are trying to perfect the art of modi-
fying genetic expression in human embryos. It follows on from a
similar publication last year, also from China, which demon-
strated... 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 selec-
tion of a normal embryo during in vitro fertilisation for couples
who both carry genes for a disorder, such as cysticibrosis.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 BernieTuch isDirector of the NSW Stem CellNetwork and an Honorary Professor
at theUniversity of Sydney.
“This paper is clearly looking toward human reproductive uses of
this technology, about which there has beeninsuicient national
and international discussion and debate,both within the scien-
tiiccommunity and between thescientiic community andthe
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 thedii-
culties of applyingCRISPR/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 accu-
racy and eiciency 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 eicacy and improving the accuracy of gene editing
in human embryos.
“The newly published work was performed with institutional
ethics approval, and further conirms that the ield does not have
the correct technical know-how to begin proof-of-principle exper-
iments to correct genes in pre-implantation embryos for therapeutic
beneit. 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 beneit tosociety.”
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 CCR5gene which render those individuals
resistant to HIV infection. Thus, using gene editing to create
individuals with the CCR5mutation would provide natural
protection against HIV.
“The new study follows essentially the same path as the irst
study; using the CRISPR/Cas9 gene-editing system in tripro -
nuclear 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 irst group. This indicates the reproducibility
of the science... [and] should inspire conidence in the public.
However, this group of researchers also reproduced another inding
described by the irst 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 informa-
tive 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.40 | MAY 2016
EXPERT OPINION Australian Science Media CentreSecond Genetically Modified Human Embryos Created
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.
The original paper in the Journal of Assisted Reproduction and Geneticscan be downladed from http://tinyurl.com/jzh3xbp