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11 December, 2018 10:21:36 AM

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Controversy surrounding gene-editing of babies

The goal of the editing was to confer resistance to HIV by modifying the CCR5 gene, the protein doorway by which HIV enters human cells
Mohammed Abul Kalam, PhD
Controversy surrounding gene-editing of babies

A scientist in China claims to have produced the world’s first genome-edited babies by altering their DNA to increase their resistance to HIV. Aside from the lack of verifiable evidence for this non peer-reviewed claim, this research is premature, dangerous and irresponsible.
He Jiankui from the Southern University of Science and Technology in Shenzhen said he edited the DNA of seven embryos being used for fertility treatment, so far resulting in the birth of one set of twin girls.

He says he used the tool known as CRISPR to delete the embryos’ CCR5 gene (C-C motif chemokine receptor 5), mutations in which are linked to resistance to HIV infection.
The media is buzzing with the surprise news that a Chinese researcher, Jiankui He, has created the world’s first genome-edited twins. He did this, ostensibly, to provide resistance to HIV, the virus that causes AIDS.
Prof. He, reportedly working with former Rice University supervisor Michael Deem, capitalized on work in 2012 by Jennifer Doudna and Emmanuel Charpentier, who introduced a new and easier way of altering the DNA of human and non-human organisms using CRISPR-Cas9 technology. He also built upon the work of molecluar biologist Feng Zhang, who optimized this genome editing system for use in human cells.

He’s claim moves human germline genome editing from the lab to the delivery room — something other scientists might have been thinking about despite ethical concern. Jiankui He explains why his lab edited the genome of twin baby girls, Nana and Lulu, when they were embryos.

If true, this is a significant advance in genetic science, but there are some very serious problems with this news. First, the research has not yet been published in a peer-reviewed journal so we cannot be sure of the exact details of what has been done. Instead, the scientist made the claims to the Associated Press news organization, and the journalists involved haven’t been able to independently verify them. The parents of the allegedly gene-edited babies declined to be interviewed or identified.Second, we know there can be significant problems with using existing gene-editing technology on human embryos. The main two issues are mosaicism, where the edited DNA does not appear in every cell of the embryo, and off-target effects, where other parts of the genome may also have been edited with unknown consequences.

The scientific community has expressed widespread condemnation ofHe’s decision to initiate a pregnancy using genetically modified embryos — as “dangerous, "irresponsible” and “crazy.” What if mistakes are made? How can we be sure this powerful technology will benefit humankind? Are we ready for the consequences of genetically engineering our own evolution?

We argue that we cannot allow individual scientists to decide the fate of the human genome. Heritable human genome editing poses a significant existential threat because changes may persist throughout the human population for generations, with unknown risks.

We must commit to inclusive global dialogue — involving experts and the public — to develop broad societal consensus on what to do with genetic technologies.

Possible mutations or forced sterilization:He announced to the world that he edited the genome of human embryos for seven couples using CRISPR-Cas9 technology. According to He, two of these embryos resulted in a pregnancy, and twin girls (Lulu and Nana, which are pseudonyms) were born.

The goal of the editing was to confer resistance to HIV by modifying the CCR5 gene (the protein doorway by which HIV enters human cells). He claims that these edits have been verified in both twins and this data has been looked over and called “probably accurate”” by George Church, a world-renowned Harvard geneticist.

Evidence suggests, however, the procedure was unnecessary, is unlikely to provide benefit and could even cause harm. Although the father of Lulu and Nana was HIV positive, it is unlikely that he would have passed this disease to his children using standard IVF procedures.

The children born of genome editing are genetic mosaics with uncertain resistance to HIV and perhaps decreased resistance to viral diseases like influenza and West Nile. This is because the CCR5 gene that He disabled plays an important role in resistance to these diseases.

As well, there is the possibility of unintended mutations caused by the CRISPR procedure. These health risks cannot be overstated, as the repercussions for these twin girls, in terms of their susceptibility to infectious diseases or cancer will likely be a cause for concern throughout their lives.

Another uncertain consequence for the twins concerns their reproductive health and freedom. As they approach reproductive age will they face the possibility of “forced” sterilization to prevent their edited genes being passed on to future generations?

Before genome editing becomes a clinical treatment, it is essential that scientists resolve both of these issues and eliminate other potential adverse effects on the embryo. We need comprehensive studies to show that genome editing is not going to cause harm to the future people it helps create. Any children born as a result of genome editing will also need long-term follow up. It would be vital to see the preliminary work that He has done to confirm that his technique has eliminated mosaicism and off-target effects, and it is surprising that he has not published this.

There is also a question over why gene-editing was used to tackle the particular issue of HIV transmission in this case. The reports suggest that the couples involved in the study were made up of HIV-positive men who had the infection under control and HIV-negative women. The risk of transmission of HIV for these couples would have been negligible, and there are well-established ways to prevent HIV transmission to the offspring of HIV-positive couples.

Do we really need gene editing?Most reports suggest that the potential main use of genome editing would be therapeutic genome editing to prevent the transmission of genetic diseases, such as cystic fibrosis. In most cases, couples at risk of transmitting a genetic disease to their children are able to prevent transmission using established techniques of screening before birth or even before an embryo is implanted via IVF. So perhaps editing embryos for therapeutic reasons is not the way forward.

Designer babies by powerful elites:With the Genetic Genie out of the bottle, we have to ask whether we need any more time to reflect on the ethics.A just and fair society is one with less disparity and more justice. A predictable consequence of allowing individuals to genetically modify their children will be greater disparity and greater injustice — and not only because of limited access to genome editing technology.

Whether He’s claims are true or not, this whole situation is a disservice to the entire field of research, and to potential future recipients of CRISPR-based therapies.

Finally, there is the wider ethical debate, which the scientist in this case has chosen to ignore. As a Medical Sociologist, Research Ethicist and Board Member of Institutional Review Board (IRB), my conclusion is that we need a public debate before gene editing on embryos was carried out because this procedure takes reproduction to a new level. With all this in mind, any research in this area needs to be peer-reviewed and published in the scientific literature, with all the necessary preliminary work, so that we can make a valued analysis of the technique. In bypassing this process, He has made our job much harder.

The writer is former Head, Department of Medical Sociology,

Institute of Epidemiology, Disease Control & Research (IEDCR)

Dhaka, Bangladesh

E-mail: med_sociology_iedcr@yahoo.com

SHK

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Editor : M. Shamsur Rahman
Published by the Editor on behalf of Independent Publications Limited at Media Printers, 446/H, Tejgaon I/A, Dhaka-1215.
Editorial, News & Commercial Offices : Beximco Media Complex, 149-150 Tejgaon I/A, Dhaka-1208, Bangladesh. GPO Box No. 934, Dhaka-1000.

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