1. In November 2018, He Jiankui revealed that he used CRISPR gene-editing to genetically modify twin babies, Lulu and Nana, born in late 2018. 2. He claims he disabled the CCR5 gene to make the babies resistant to HIV, as their father was HIV positive. However, He failed to receive proper ethics approval and conducted unsafe and unethical human experimentation. 3. He's actions faced significant backlash from the scientific community due to violations of ethical standards and risks to human research subjects.

1. BIT4005: Genomics
Digital Assignment
He Jiankui Affair: a case study
Team members:
Poornendu C - 18BBT0057
Soham G - 18BBT0058
Rucha N - 18BBT0083
Kritika S - 18BBT0211

2. The Incident
On November 25th 2018, the world discovered that He
Jianukui had used the Crispr gene-editing technology to
edit two babies. The incident took place in the case of an in-
vitro fertilization. The father who was HIV positive and the
mother was HIV negative. He claims to have disabled a
gene called CCR5, which encodes a protein that allows HIV
to enter cells.
He used forged ethics-review documents during
recruitment of participants and swapped blood samples to
skirt laws against allowing people with HIV to use assisted
reproductive technologies.

3. He Jiankui was planning to reveal his
experiments and the birth of Lulu and
Nana at the Second International
Summit on Human Genome Editing,
which was to be organized at
the University of Hong Kong during 27–
29 November 2018. However, on 25
November 2018, Antonio Regalado,
senior editor for biomedicine of MIT
Technology Review, posted on the
journal's website about the experiment
based on He Jiankui's applications for
conducting clinical trial that had been
posted earlier on the Chinese clinical
trials registry. At the time, He refused to
comment on the conditions of the
pregnancy.
Retrieved from: https://www.ricethresher.org/multimedia/crispr-
graphic-dan-helmici

4. About the experiment
● In 2016, He Jiankui began experimenting with CRISPR to edit embryos of rodents, monkeys,
and humans. Some of the rodent and the monkey embryos were transferred into females
and led to live births. The human work was solely based on the embryos that were not
intended for possible birth.
● In late 2017 or early 2018, He began an effort to produce human babies from gene-edited
embryos. Through a Beijing-based organization intended to help Chinese people with HIV, he
recruited couples for the experiment, couples where the father was HIV-positive, and the
mother was not. Eight couples agreed to participate, although one subsequently withdrew. Of
the remaining seven couples, five women had a total of 13 embryos transferred for
implantation,12 two of whom got pregnant.
● By early april 2018, one of the women was pregnant with twins. In october, the woman gave
birth to two non-identical twin girls. The girls were named ‘Lulu’ and ‘Nana’.
● The girls were healthy by the late november, when he announced the experiment on stage
(27 November).

5. ● At the embryonic stage, the babies were injected with a CRISPR construct that was intended
to cause a 32-base-pair deletion in a gene called CCR5, which is found on chromosome 3.The
version of the gene with this deletion is called CCR5Δ32.This deletion would make the gene
produce non-functional copies of the CCR5 protein.Almost all humans have two proper
copies of the CCR5 gene, one each on the copies of chromosome 3 they inherit from their
mothers and their fathers.
● A few people(especially north europeans)in the world, carry one proper copy and one copy of
the CCR5Δ32 variant, with the 32-base-pair deletion. And very few humans, again most often
in Northern Europe, are known to carry two copies of the mutant gene variation.
● In his experiment, he sought to produce humans who could not contract AIDS(because they
had the 32-base-pair deletion that led to a non-functional CCR5 protein). He was trying to
reproduce the phenotype of a specific mutation in the gene, CCR5-Δ32, that few people
naturally have and that possibly confers innate resistance to HIV.

7. 1. They took sperm and eggs from the couples, performed in vitro fertilisation with the eggs and sperm, and then
edited the genomes of the embryos using CRISPR/Cas9.
2. The editing targeted a gene, CCR5, that codes for a protein that HIV uses to enter cells,instead of introducing the
known CCR5-Δ32 mutation, He introduced a frameshift mutation intended to make the CCR5 protein entirely
nonfunctional.
3. He used a preimplantation genetic diagnosis process on the embryos that were edited, where three to five single
cells were removed, and fully sequenced them to identify chimerism and off-target errors. He says that during
the pregnancy, cell-free fetal DNA was fully sequenced to check for off-target errors, and an amniocentesis was
offered to check for problems with the pregnancy.
4. As for the results, he claimed that no or very few supposed off-targets were detected. The editing efficiency was
claimed to be around 32% and majority of the embryos were found to be mosaic.

8. Ethical issues with the experiment
● Dr. He claimed he had ethics approval from Shenzhen Harmonicare Women’s and Children’s
hospital, but he did not claim approval from his home institution or the four (unnamed)
hospitals that provided the embryos. The article quotes Dr. Liu Zhitong, the head of
Harmonicare’s ethics panel, as saying ‘we think this is ethical ’.
● At the time of writing, the data describing these experiments had yet to be peer reviewed.
Irrespective of the problematic nature of science by press announcement, the methods,
timing and procedures used by He in his clinical trials violate several ethical norms,
including international consensus guidelines, national regulations and well-established
principles of bioethics. He is not a medical doctor, but rather received his doctorate in
biophysics and did postdoctoral studies in gene sequencing; he lacks training in bioethics,
responsible conduct of human research, or a background in evolutionary biology that might
have informed him of some of the glaring deficiencies in his work.

9.  Alta Charo, who specializes in law and bioethics at the University of Wisconsin–Madison,
agrees that it was unclear how any of these individuals could have effectively blown the
whistle. Had the research been conducted in the United States, a scientist could have
contacted the Office for Human Research Protections or the Office of Research Integrity.
But China has different values and opaque regulations. “If it is happening elsewhere, a
scientist may be wholly unfamiliar with the norms and laws in that foreign country,” says
Charo.
 But He’s actions seem to have embarrassed China, judging by the removal of references to
him from government websites and censorship on social-media platforms such as
WeChat. (It was one of the top ten censored topics of 2018.) He’s actions might prompt
China to develop new regulations and better institutional oversight, says Leigh Turner, a
bioethicist at the University of Minnesota in Minneapolis.
 The investigations into He and others — and any punishments they might face — could
influence where researchers choose for their next attempts, says Turner. If He’s
collaborators outside China are subjected to sanctions, that might help to limit researchers
based in countries with strict laws from working outside those jurisdictions.

10. 10 major ethical violations by He Jianukui in the
field of genome editing
1. He’s work is a violation of an international consensus on if, whether, or when the
editing of human embryos should be permitted. At the First International Summit
on Human Gene Editing in 2015 in Washington, DC, the organizing committee
released a statement1 that it would be irresponsible to proceed with any clinical
use of germline editing unless and until
(i) the relevant safety and efficacy issues have been resolved, based on
appropriate understanding and balancing of risks, potential benefits,
and alternatives, and
(ii) there is a broad societal consensus about the appropriateness of the
proposed application.

11. 2. He has not reported prior studies of CRISPR edits on embryos of mice, primates and
humans. There is a void in the scientific literature as to He’s prior work on editing
embryos. His English language publications (19 in PubMed) list only a single
publication involving CRISPR editing.
3. Reporting of off-target effects and highlighting of the risks of gene-editing embryos
was insufficient. Off-target and undesirable ‘on-target’ effects are commonplace with
the use of CRISPR–Cas9 and represent the most prevalent risks to an organism.
4. He failed to gather sufficient information and follow scientific consensus on the
minimal risks that would make gene-editing of embryos permissible. No references
are given in He’s writings, website or public statements on the consensus or lack
thereof that there are minimal risks in undertaking gene editing of embryos at the
current state of knowledge.
5. He did not comply with the national ethical guidelines in China for embryo research.
In 2003, China issued guidance to IVF clinics that prohibits the implantation of
embryos used in research.

12. 6. He failed to work within the ethical framework of his own university (The Southern
University of Science and Technology).
7. Enhancement—widely acknowledged as the most ethically problematic frontier of
germline gene editing—took precedence in He’s experiments over curing a life-
threatening disease.
8. He engaged in undue inducement of parents. Ethical guidelines on recruiting people
into clinical trials recognize the problem of extravagant inducements. He
communicated to prospective parents that his trial would cover IVF payments,
supportive care and a daily allowance.
9. The informed consent form that he submitted to his research subjects was a 23-page
document. It contained many technical terms, had no discussion about the meaning
and significance of off-target effects or undesirable on-target changes on the child.
10. He did not inform parents in the trial of his conflicts of interest

13. Concerns specific to applications other than preventing
transmission of genetic variants known to be associated with
serious illness or disability
 Commodification of children
 Creation of social pressure to modify children to maintain a level playing
field with children modified by other parents
 Exacerbation of social inequality based on access to the technology
 Unknown and unpredictable risks of creating novel genome modifications
 Potential to create harm that will extend to multiple generations
 Potential for state-imposed eugenic applications
 Potential for criminal applications

14. Concerns perpetrated by the society:
• Disrespect of DNA as human heritage
• Challenging God’s role in creation
• Lack of informed consent by the child and future generations affected by the editing
• Negative impact on individuals with disabilities related to genetic variants
• Perceptions of parental negligence for deciding against performing genome editing
Retrieved from: https://culturico.com/2019/03/13/is-the-world-ready-for-crispr-babies/

16. References
● David Cyranoski. March 11, 2019. The CRISPR-baby scandal: what’s next for human
gene-editing. Nature. https://www.nature.com/articles/d41586-019-00673-1
● Jiankui He talking about human genome editing.
https://www.youtube.com/watch?v=llxNRGMxyCc
● Bhavna Karnani. March 13, 2019. Is the world ready for CRISPR babies? Culturico.
https://culturico.com/2019/03/13/is-the-world-ready-for-crispr-babies/
● Dan Helmici. The Rice Thresher. https://www.ricethresher.org/multimedia/crispr-
graphic-dan-helmici