GERMLINE EDITING — A BRIEF RECAP
In April 2015, a Chinese team first reported using CRISPR-Cas9 on human embryos. Experiments were conducted on 86 discarded embryos obtained from a fertility clinic. Researchers encountered serious obstacles. In December 2015, Congress passed legislation specifying no public funding could be used for research “in which a human embryo is intentionally created or modified to include a heritable genetic modification.” In February 2016, a team led by developmental biologist Dr. Kathy Niakan of the Francis Crick Institute in London used CRISPR-Cas9 to disrupt the production of a protein called OCT4 in human embryos in order to better understand embryonic development. In 2017, Dr. Shoukhrat Mitalipov, Director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University (OHSU),
secured private funding and edited human embryos to repair a mutation in a gene called MYBPC3, which causes a deadly heart disease – hypertrophic cardiomyopathy (HCM), a thickening of the heart muscle. In July 2018, the United Kingdom’s Nuffield Council on Bioethics determined that heritable genome editing could be “ethically acceptable in some circumstances.” In August 2018, Chinese researchers announced that CRISPR base editing had been used to correct a single DNA letter – a “C” to a“T” in the gene FBN1 that causes Marfan syndrome, an incurable connective tissue disorder that affects about 1 in 5,000 people. Success was achieved in 16 out of 18 embryos, a significant improvement over Dr. Mitalipov’s results (42 out of 58). But no event has impacted the discussion over germline editing as much as the announcement made in Hong Kong in November 2018 (below left).
Chinese biophysicist announces birth of the first CRISPR-edited babies In November 2018, on the eve of the Second International Summit on Human Genome Editing in Hong Kong, Dr. He Jiankui, a Chinese biophysics researcher and Associate Professor in the Department of Biology at the Southern University of Science and Technology (SUSTech) in Shenzhen, announced the birth of twin girls (Lulu and Nana) from embryos whose genomes had been edited using CRISPR. Initially, Dr. He did not present any solid proof that this experiment had, in fact, taken place, which cast doubt on his motives and triggered international concerns from scientists. The world scientific community reacted with shock, outrage, and nearunanimous condemnation. Summit Chairman and Nobel Laureate Dr. David Baltimore called Dr. He’s experiment “irresponsible” and criticized his lack of transparency. Dr. Feng Zhang called for a moratorium on gene-edited babies. Dr. Jennifer Doudna said in a statement that “this work reinforces the urgent need to confine the use of gene editing in human embryos to settings where
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Dr. He Jiankui addresses the Second International Summit on Human Genome Editing in Hong Kong. a clear unmet medical need exists, and where no other medical approach is a viable option, as recommended by the National Academy of Sciences.” And NIH Director Dr. Francis Collins declared in a statement that “this work represents a deeply disturbing willingness by Dr. He and his team to flout international ethical norms.” Concern was also expressed over the fact that several Western scientists knew of Dr. He’s research, and it was felt they had not done enough to stop him. In January 2019, it was confirmed that Dr. He’s experiments had, in fact, taken place – and the twin girls were under medical observation. An additional
pregnancy was also confirmed. That same month, Chinese investigators released their initial findings, promising stiff penalties, and Dr. He’s university fired him. Tests confirmed that one of the twins will be resistant to HIV because the gene edits silenced both copies of her CCR5 gene. The other twin might still be susceptible to infection because one copy of her CCR5 gene was left intact. In March, Chinese officials drafted stricter rules for human gene editing. According to a May 2019 Wall Street Journal article, Dr. He had originally been investigating editing a gene that can offer protection from familial hypercholesterolemia, a rare cholesterol-related disease that can cause broken bones in children. He changed his mind after visiting a village where he saw HIV-positive families facing discrimination. In China, children born to infected individuals are not able to attend regular schools. Dr. He saw the trial as a way to use science to fight that injustice and, at the same time, bring glory to China, the Journal reported.
Russian biologist renews controversy with two plans to create more CRISPR-edited babies Dr. Denis Rebrikov, who heads a genome-editing laboratory at Russia’s largest fertility clinic, the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in Moscow, told the journal Nature he plans to use CRISPR to edit the CCR5 gene in embryos – the same gene Dr. He Jiankui targeted – to create HIV-resistant babies. Dr. Rebrikov explained he hopes to take a different approach than Dr. He, who conducted his experiments using sperm from HIVpositive fathers. Dr. Rebrikov plans to implant edited embryos into only a subset of HIV-positive mothers who do not respond to anti-HIV drugs as the risk of the mother transmitting the infection to the child is far greater. In response, Nature has tried to rally opinion to stop him. “Time is of the essence,” Nature warned. Most scientists remain adamant that there is no justification for editing the CCR5 gene in embryos because the risks don’t outweigh the benefits. In addition, New Scientist reported that Dr. Rebrikov
Dr. Denis Rebrikov
also intends to use CRISPR to give deaf couples babies who can hear. He has found five pairs of deaf parents who have agreed to let him use CRISPR technology to ensure that children born from their edited embryos would not inherit a deafnesscausing mutation in the GJB2 gene. Dr. Rebrikov told Nature he won’t actually create any CRISPR babies unless the Ministry of Health of the Russian Federation gives him the green light. In 2018, Vladimir Putin allocated roughly $2 billion for genetic research and named Dr. Maria Vorontsova, an endocrinologist who some say is Putin’s oldest daughter, to the 30-person panel overseeing the work – an area of study Putin has said will “determine the future of the whole world.”