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First genome editing of normal human embryos

Dr Katie Howe
Progress Educational Trust
19 March 2017
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[BioNews, London]

Chinese scientists have successfully used genome editing to correct mutations in viable human embryos for the first time.

The study used CRISPR technology, which has previously been used to edit genes in non-viable human embryos. These attempts had very low success rates but it was not known if this was because the embryos had an extra set of chromosomes.

'[This study] does look more promising than previous papers,' Dr Fredrik Lanner of the Karolinska Institute in Sweden told New Scientist. Dr Lanner's team is also using CRISPR to edit genes in human embryos.

The team, led by Jianqiao Liu at the Third Affiliated Hospital of Guangzhou Medical University, used eggs leftover from IVF procedures and fertilised them with donor sperm from two men to create six embryos. One of the sperm donors had a mutation called β41-42, which causes beta-thalassemia, while the other donor had a mutation in the G6PD gene. This is a common cause of favism – a disorder in which eating foods like broad beans can trigger the destruction of red blood cells.

Two of the resulting embryos had mutations in the G6PD gene, and four embryos had the β41-42 mutation. The researchers injected them with the CRISPR machinery and allowed them to develop for two days. They then analysed the embryos' DNA to check whether the mutations had been successfully corrected.

The mutation in the G6PD gene was successfully repaired in one embryo. In the other embryo, it was corrected only in some cells, forming a mosaic embryo.

The β41-42 mutation was also only partially corrected in one embryo, forming another mosaic. CRISPR induced another mutation in another embryo, and the technique did not work at all in the two remaining embryos.

Speaking to New Scientist, Professor Robin Lovell-Badge of the Francis Crick Institute described the results as 'encouraging'. However, he warned that the numbers are far too low to make strong conclusions.

Before the technology could be used in the clinic, researchers would need to find a way to prevent mosaic embryos, for example by editing genes in sperm and eggs before IVF, rather than editing embryos.

There are also many ethical concerns over the use of genome-editing technologies. A recent report by the US National Academy of Sciences advised that genome editing should be be restricted to genes that are known to cause or predispose people to serious conditions, and should only be carried out the absence of other alternatives – for example when none of a couple's embryos will be free of inherited disease.

The research was published in the journal Molecular Genetics and Genomics.



CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein
Molecular Genetics and Genomics | 01 March 2017

First results of CRISPR gene editing of normal embryos released
New Scientist | 09 March 2017
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Responses (1)
Response from Ke-Hui Cui 28 March 2017
CRISPR Is For Human Research Rather Than Human Reproduction The low success rates of the reported research results were foreseeable when molecular biological techniques were practised with human embryos, because the corrected target base of DNA is not possible to be focused in living cells, and a correct base to base matching rate is not possible to be 100% in molecular biological techniques. It is interesting to perform this kind of research in human. However, if the aim of the research is for producing human babies (i.e. human reproduction) with the CRISPR technology, please responsibly read the following comments first: HUMAN BEINGS SHOULD NOT BE CHANGED IN HEREDITY Now human beings are facing two major challenges: One is: human overpopulation in this world has over-used earth resources (air, water, plant field and ores, etc.) which should be kept on for human offspring using. Second is: Human beings will be changed in heredity greatly and easily by new artificial techniques, (such as A. mitochondrial replacement techniques (MRT) [for example: mitochondrial Augment Program by OvaSciences, which suggested artificially extracted mitochondria should be injected into every eggs to obtain human babies]; B. human sperm and oocytes produced from human stem cells; C. human gene(s) to be modified in human sperm, oocytes and embryos by gene CRISPR techniques; D. human cloning; … etc.,) which are all aimed at embryo transfer to produce sub-human being babies. John Zhang (New Hope Fertility Center in New York City) announced the birth of three parents’ child, which was really deliberate by John Zhang aimed as a “pioneer” similar to IVF and PGD. He exposed this point when he talked to the Chinese reporter. However, the key different point between MRT and IVF or PGD is: MRT changes human beings in heredity or in genetics, which did not naturally happen in human history; while IVF and PGD do not change human beings in heredity. The birth report by John Zhang and some related propaganda are misleading in human history of natural development. First, changing human beings in heredity to cure human disease for having a child is not scientific and not logical. Human beings is far, far away to that stage that the heredity should be changed for further survival. (No any patient should be treated individually as not belonging to the society of human beings.) If now we begun to change human beings in heredity as John Zhang and OvaScience suggested, human beings would really need to change the heredity for further survival in two or three centuries or much earlier, rather than over 1 million years. Thus John Zhang is short-sighted and OvaScience businessmen is disturbance in human reproductive medicine. Second, concept of science from Merriam-Webster online dictionary is: “Knowledge about or study of natural world based on facts learned through experiments and observation”. The birth report is not based on natural world, but to change natural human beings into artificial sub-human beings. Thus it is not a true science, but a pseudoscience. Human create science to serve human beings rather than to change human being. Third, patients have their dignity. Countries have their dignity. Human beings also have their dignity. Human dignity covers patient dignity and country dignity. Human dignity is the superior dignity than any other kinds of dignity. In human dignity, the natural heredity is the highest dignity of our human beings and is the cornerstone of human beings, which makes human beings to be different from animals. Thus, human heredity should not be manipulated as animal by pseudoscientists, no matter how safe or not safe, birth or five stillbirth. Human beings in heredity should be kept to be green as what we wish to keep the world to be, and should be much, much stricter. Fourth, severe gene mutation and chromosomal abnormalities in new born babies are about 1%. That is a natural phenomenon. Changing human being in heredity will not change this natural phenomenon, because new mutations and new chromosomal abnormalities will happen all the time. However, preimplantation genetic diagnoses and prenatal diagnoses can obviously reduce this percentage. Fifth, trend in the world changed: In last 400 years, industry and science developed fast, especially in recent 70 years. Antibiotics and other science greatly improve human life expectancy. Now human population is more than three times of that time of 70 years ago, and still going up. Artificial fertilizer and insecticide let us have enough food to eat; artificial cloth let us have enough clothes to wear; cars run in the cities and highway. In those years, “artificial” is a positive term and a strong trend. The birth of cloned sheep Dolly was the apex of “artificial”. Mitochondrial replacement techniques in human reproduction followed next year. People cheered. However, in a very short time, Dolly showed a lot of “reprogramed” problem. And the fact of MRT, which showed the human genes had been changed, exposed. Criticism about MRT began, which was recognized as “negative” in reproductive medicine at that time, because MRT is a “science”. Nevertheless, facts were relentless. A lot of true negative news about the word “artificial” reported in our daily life: Air is polluted by industrialization; Plant field turned hard by artificial fertilizer; Water and food is contaminated by insecticides; Men’s sperm count is going down by all kinds of artificial chemical substance. They showed that the earth is limited for resources. It has been out of the limit for natural recirculation and cleaning. “We want green (natural environment)” has suddenly become a popular and positive slogan in our lovely world in these 15 years opposite the last 400 years. The word “artificial” lost its luster, from positive meaning changing to negative meaning, which is replaced by the word “natural” or “green” as positive trend in a lot of fields of our daily life and in some field of reproductive medicine. People begin to realize MRT to change human beings in heredity is negative, because it crossed redline of normal and natural human Genetics, which will change our offspring forever. Sixth, using naïve and wrong British congress decision to challenge severe US FDA regulation is not appropriate, while an American physician even worked in Mexico and gave the report in US. No people believes US FDA is nothing when facing activities of anti-human heredity. Cooperated with US FDA and State Department, Chinese government has banned this kind of practice of changing human beings in China in 2003 since John Zhang’s first report of similar practice with a five-stillbirth crime in China. Further international cooperation and international regulations are needed for protecting human beings from being changed in heredity. Please also read: 1. “CHANGING HUMAN BEINGS BY MRT IS MISLEADING AND NOT SCIENTIFIC” published on 05 December 2016 comment for “Expert panel approve cautious use of mitochondrial donation in the UK” response on 19 December 2016. 2. “CHANGING HUMAN BEINGS IN HEREDITY IS MISLEADING AND INFAMOUS” published on 01 November 2016 comment for “ ‘Three-person babies’ grow up into healthy teenagers” response on 07 November 2016. 3. “Fact Sheet 2. Re: Not Suitability To Use Artificially Created, Modified Or Reprogrammed Human Eggs (Or Sperm) To Produce Babies” published on 25 October 2016 comment for “Functional mouse eggs made from artificial stem cells” response on 11 November 2016. Ke-Hui Cui M.D., Ph.D.
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