UC Berkeley Study Shows CRISPR Babies have Higher Death Risk

UC Berkeley Study Shows CRISPR Babies have Higher Death Risk

Cami Rosso 04/06/2019 6

Today researchers at the University of California, Berkeley (UC Berkeley) released a study in Nature Medicine that shows an estimated 21 percent increase in mortality rate in individuals with the CCR5-∆32 mutation—demonstrating the potential lethal outcome of the human germline editing by a Chinese scientist last year.

Human germline editing is the process of editing the genome so that the change is heritable. This involves the genetically changing the human germ cells—reproductive cells like the human egg and sperm. In November 2018 He Jiankui formerly at the Southern University of Science and Technology (SUSTech) in Shenzhen, China, announced the world’s first live birth of humans with edited CCR5 genome during his presentation at the Second International Summit on Human Genome Editing held at the University of Hong Kong.

Jiankui’s work was criticized worldwide. Bioethicists, scientists, and critics point out that the scientist violate scientific practices and ethics–human germline editing is a risky endeavor with unknown consequences. Jiankui’s November 2018 article on ethics was retracted 12 weeks later by The CRISPR Journal for failing to disclose conflict of interest. “The authors intentionally hid from us the fact that they were conducting clinical research on germline editing, and that babies had been born,” stated The CRISPR Journal’s chief editor, Rodolphe Barrangou in GEN. In January of 2019Jiankui was fired from his university.

Individuals with the CCR5-∆32 (also called CCR5-delta 32) genetic mutation are naturally resistant to HIV infections because the HIV virus is not able to enter the cells of the immune system. Jiankui modified the CCR5 gene using CRISPR–Cas9 with the goal of synthetically recreating the natural CCR5-Δ32 mutation.

CRISPR-Cas9 (Clustered Regularly-Interspaced Short Palindromic Repeats) enables researchers to rearrange genes quickly and easily. Jennifer Doudna at the University of California, Berkeley, and microbiologist Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Berlin and Umeå University in Sweden, made scientific history in 2012 by publishing pioneering work that demonstrates that the Cas9 enzyme can be directed to cut specific sites in isolated DNA— a major breakthrough in genomic editing. Following a year later, Feng Zhang at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, published a study demonstrating the use of CRISPR–Cas9 for genetic editing in the cells of mammals.

Jiankui took an unvetted and nontransparent approach that is not in accordance to commonly-held global scientific practices. When Jiankui made his announcement last fall, he did not have an associated scientific paper published in a scientific journal to substantiate and detail the study’s methodology and outcomes. Research papers published in peer-reviewed, top-tier scientific journals are investigated by reputable scientists who are experts in the respective field, and therefore carries gravitas as a trusted source. Instead, he opted to post YouTube videos online that lacked specificity of how the research was conducted.

Twins girls Lulu and Nana were born with their genomes edited according to Jiankui in his online videos. “100 million people naturally have a genetic variation that disables CCR5, protecting them against HIV,” said Jiankui. He viewed his human germline gene editing as an attempt to recreate the natural variation by removing “just a few DNA letters.”

However, Jiankui did not succeed in recreating the CCR5-Δ32 mutation. “He was unable to duplicate the natural mutation, but appears to have generated a similar deletion that would also inactivate the protein,” according to a June 3, 2019 report released in Berkeley News. “One of the twin babies reportedly had one copy of CCR5 modified by CRISPR-Cas9 gene editing, while the other baby had both copies edited.”

The UC Berkeley research team of Rasmus Nielsen, professor of integrative biology, and postdoctoral fellow Xinzhu Wei, conducted detailed statistical analysis on the genotyping and death register of 409,693 database records of people with British ancestry from UK Biobank database.

“We might expect that the Δ32 mutation is deleterious in the homozygous state based on previous reports in smaller data sets, which show that individuals with the Δ32/Δ32 genotype have increased mortality when infected by influenza,” wrote the researchers in Nature Medicine.

The UC Berkeley research study showed an estimated 21 percent increase in the all-cause mortality rate in individuals who are homozygous for the Δ32—a significant finding that demonstrates the risk of human germline editing.

“Beyond the many ethical issues involved with the CRISPR babies, the fact is that, right now, with current knowledge, it is still very dangerous to try to introduce mutations without knowing the full effect of what those mutations do,” stated Nielsen in Berkeley News. “In this case, it is probably not a mutation that most people would want to have. You are actually, on average, worse off having it.”

Copyright © 2019 Cami Rosso All rights reserved.

References

Rosso, Cami. “Why Crispr-Cas9 is Pandora’s Box.” Medium. March 21, 2016.

Wei, Xinzhu, Nielsen, Rasmus. “CCR5- Δ32 is deleterious in the homozygous state in humans.” Nature Medicine. June 3, 2019.

Sanders, Robert. “CRISPR baby mutation significantly increases mortality.” Berkeley News. June 3, 2019.

Cyranoski, David. “CRISPR-baby scientist fails to satisfy critics.” Nature. 28 November 2018.

LeMieux, Julianna. “He Jiankui’s Germline Editing Ethics Article Retracted by The CRISPR Journal.” GEN. February 20, 2019.

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  • Alex Gonzalez

    I hope they figure out soon how to heal people with CRISPR.

  • Iris Phelps

    Wonder if I could fix my diabetes

  • Joey Russell

    I want my babies to have a tail and wings :D

  • Karen Venaglia

    Interesting

  • Liam Dixon

    America will spend the next 30 years trying to figure out how to make as much money from this rather than curing diseases.

  • Raheel Mahmood

    If we can edit out genetic diseases, we absolutely should and it would be unethical not to for those who have the means.

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Cami Rosso

Science Guru

Cami is a founder of three companies in high-tech consulting, global venture capital, and strategic marketing. She founded her first company during college and had a state branch of the Department of Aviation as her customer. She was a Kauffman Fellows semi-finalist. She has worked in Silicon Valley, Wall Street and globally for great companies like Apple, Morgan Stanley, PepsiCo, Adobe, and Oracle, to name a few. Cami was an American business delegate to the APEC/PECC IT summit of world leaders. She was an invited guest to meet an ambassador and diplomats to a Mission of the United Nations. Cami's speaking experience includes TV, radio, academia and industry conferences. She earned an MBA from IMD in Switzerland and a certificate in Marketing Innovative Technologies at the Harvard Business School Executive Education Program. She was recognized by The Financial Times and Radio Switzerland for her contribution to an award-winning team humanitarian project for children in UNHCR refugee camps.

   

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