Skip directly to content

Treatment Action Group Statement on the Reported Birth of Twins with Edited CCR5 Genes

New York, November 26, 2018 – Treatment Action Group (TAG) decries the claimed use of CRISPR technology to edit genes for the HIV co-receptor CCR5 in human embryos for implantation.

Yesterday, He Jiankui, an Associate Professor at the South University of Science and Technology of China, posted a video to YouTube claiming to have employed CRISPR/Cas9 technology to edit the genetic code of embryos, leading to the birth of twins with mutated genes for the HIV co-receptor CCR5.1  The announcement has triggered extensive media coverage and ignited a firestorm of controversy.

“Treatment Action Group joins with the scientists and ethicists who are condemning the work as unethical, unjustified, and potentially dangerous,” said Richard Jefferys, TAG’s Basic Science, Vaccines, and Cure Project Director.  “The risks of prematurely experimenting in human embryos for implantation with an insufficiently understood intervention far outweigh the potential benefits, especially as HIV already has multiple rigorously studied and safe prevention and treatment options.” 

“While we recognize with indignation that the full array of quality HIV treatment and prevention options is not routinely accessible in China, the answer is to make these interventions available, not to take extremely risky measures that further jeopardize human health and rights,” said Mike Frick, TAG’s Tuberculosis Project Co-Director, who, prior to joining TAG, worked with HIV activists in China. “All people have the right to enjoy the benefits of scientific progress, but for this human right to be upheld, all research, regardless of where it takes place, must follow ethical standards of scientific conduct, including free and informed consent and protections for vulnerable populations."

TAG’s primary concerns about this purported experiment and its claimed results include:

1. The existence of safe, established options for preventing HIV transmission at conception, in utero, and throughout life raises the risk-benefit ratio bar that experimental alternatives must clear.  He’s video could be misinterpreted as suggesting that the experiment allowed a couple in which the male partner is HIV-positive to have HIV-negative offspring; that is not the case, as there are established and safe techniques that can be used for that purpose. There are also well-established, safe methods for preventing HIV infection throughout an individual’s lifespan, including pre- and post-exposure prophylaxis.

2. The incomplete ability of the CCR5Δ32 mutation to prevent HIV acquisition calls into question the potential benefits of this intervention. 

            a. The CCR5 co-receptor protein is used by the majority of HIV strains to enter cells. Individuals who inherit the CCR5Δ32 mutation from both parents (CCR5Δ32 homozygotes), which the experiment sought to mimic, face a lower risk of acquiring HIV. But they are not fully protected because there are viral variants that gain entry into cells via a different co-receptor, CXCR4 (X4). Infection by X4-using strains is relatively rare but has been documented, and is associated with rapid CD4 T cell loss and in some cases, accelerated disease progression. 2,3

            b. If only one of the pair of CCR5 genes present in the human genome is mutated, making an individual heterozygous for the CCR5Δ32 mutation, HIV acquisition risk is not affected – a recent meta-analysis of published studies suggests it may even be slightly increased.4  In an Associated Press article, He claims that one of a pair of twins born with genes edited at the embryonic stage is homozygous for the CCR5Δ32 mutation, while the other is heterozygous.

 3. The safety of using CRISPR technology in humans is not established. It is premature to experiment with CRISPR/Cas9 technology in human embryos for implantation.

4. It is unclear if this research followed required regulatory and ethics procedures.  We do not know if the complexities of the relationship between HIV and the CCR5Δ32 mutation, or alternative options for HIV prevention, were fully explained to the participants in He’s research, or whether He sought appropriate regulatory and ethics approval.

5. This announcement was made public prior to releasing data for public scrutiny or rigorous peer-review, undermining its credibility.

6. This announcement threatens to damage legitimate progress in the therapeutic use of gene editing techniques. As Fyodor Urnov of the Altius Institute for Biomedical Sciences states in an article in MIT Technology Review: “It is a hard-to-explain foray into human germ-line genetic engineering that may overshadow in the mind of the public a decade of progress in gene editing of adults and children to treat existing disease.”5  A variety of research involving the transfer of gene-edited cells is being pursued in people with HIV, in some cases with promising results, but it does not involve altering an individual’s germline in ways that would be heritable.

TAG acknowledges that there can be cultural differences in approaches to scientific ethics, and that perception of the value of such an extreme experimental approach toward preventing HIV infection might be influenced by the degree of stigma prevalent within a society as well as the magnitude of acquisition risk. Even with this understanding, however, we believe the research He claims to have conducted is wrong and unethical, given the nature of the work.

At a minimum, the profound implications of producing gene-edited humans required a broad discussion of the approach informed by the views of scientists, potential beneficiaries, and society at large, in addition to review and approval by a reputable regulatory and ethics bodies, and fully informed consent about potential harms and benefits from participating parents. Not a secretive trial followed by a public announcement on YouTube (reportedly accompanied by the hiring of a US-based public relations representative).

TAG calls for a thorough investigation into how this experiment came to take place, including whether appropriate regulatory bodies were consulted, and the role of the US-based scientist Michael Deem of Rice University, who has stated that he was present when trial participants consented to involvement. TAG also stands with Chinese activists in calling for increased access to validated, safe treatment and prevention options in China, and for eliminating the stigma and discrimination still associated with HIV.

#          #          #

About TAG: Treatment Action Group (TAG) is an independent, activist and community-based research and policy think tank fighting for better treatment, prevention, a vaccine, and a cure for HIV, tuberculosis, and hepatitis C virus. TAG works to ensure that all people with HIV, TB, or HCV receive lifesaving treatment, care, and information. We are science-based treatment activists working to expand and accelerate vital research and effective community engagement with research and policy institutions. TAG catalyzes open collective action by all affected communities, scientists, and policy makers to end HIV, TB, and HCV.


1. https://www.youtube.com/watch?v=th0vnOmFltc
 

2. Sheppard HW, Celum C, Michael NL, et al. HIV-1 infection in individuals with the CCR5-Delta32/Delta32 genotype: acquisition of syncytium-inducing virus at seroconversion. J Acquir Immune Defic Syndr. 2002 Mar 1;29(3):307-13. Review. https://journals.lww.com/jaids/Abstract/2002/03010/HIV_1_Infection_in_Individuals_With_the.13.aspx

3. Oh DY, Jessen H, Kücherer C, et al. CCR5Delta32 genotypes in a German HIV-1 seroconverter cohort and report of HIV-1 infection in a CCR5Delta32 homozygous individual. PLoS One. 2008 Jul 23;3(7):e2747. doi: 10.1371/journal.pone.0002747. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0002747

4. Ni J, Wang D, Wang S. The CCR5-Delta32 Genetic Polymorphism and HIV-1 Infection Susceptibility: a Meta-analysis. Open Med (Wars). 2018 Oct 16;13:467-474. doi: 10.1515/med-2018-0062. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6227735/

5.  Regalado A. Chinese scientists are creating CRISPR babies. MIT Technology Review, November 25, 2018. https://www.technologyreview.com/s/612458/exclusive-chinese-scientists-are-creating-crispr-babies/